Archive for ‘Nanomedicine’

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MR-HIFU and ThermoDox to Treat Recurrent Childhood Tumors: Interview with AeRang Kim, Principal Investigator

MR-HIFU and ThermoDox to Treat Recurrent Childhood Tumors: Interview with AeRang Kim, Principal Investigator

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Children’s National Health SystemDDT Frntmttr apr06 06.2-4.qx and the Celsion Corporation (Lawrenceville, NJ) have recently announced a Phase I clinical trial in the US to determine a safe and tolerable dose of ThermoDox in conjunction with non-invasive magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU). The trial is aimed on young adults and children with recurring solid tumors.

ThermoDox technology consists of liposomes loaded with doxorubicin, a conventional chemotherapeutic drug. Liposomes are small lipid structures which can be used to encapsulate and deliver drugs through the bloodstream. While liposomal doxorubicin formulations have been available for a while, what makes ThermoDox special is that the liposomes are thermosensitive, and can release their drug payload if exposed to small temperature elevations above body temperature. This permits for highly localized release of the drug at the tumor site, which could enhance the drug effectiveness and reduce side-effects. ThermoDox is delivered into the bloodstream of the patient while the tumor site is visualized and undergoes non-invasive and localized heating using the MR-HIFU system. When the liposomes arrive at the heated tumor through the blood they rapidly release their drug payload.

Medgadget had the opportunity to discuss the clinical trial and the ThermoDox technology with the Principal Investigator for the study AeRang Kim, MD, PhD, an oncologist and a member of the solid tumor faculty at the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Health System.

 

Conn Hastings, Medgadget: Can you give us a brief overview of the proposed trial design and the hospitals and institutions that are involved?

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AeRang Kim, Children’s National Health System: This is a Phase I study of lyso-thermosensitive liposomal doxorubicin (LTLD) with MR-HIFU in children and young adults with relapsed or refractory solid tumors. This will be a dose escalation study to determine the recommended pediatric dose of LTLD combined with MR-HIFU. Once a dose is recommended, we will evaluate LTLD with MR-HIFU induced mild hyperthermia. This is a single institution study performed at Children’s National Health System, and the first study of LTLD in children.

 

Medgadget: Will the trial focus on certain types of cancer, or is any solid tumor potentially eligible for treatment?

AeRang Kim: Any malignant solid tumor is eligible, which may include but is not limited to rhabdomyosarcoma and other soft tissue tumors, Ewing sarcoma, osteosarcoma, neuroblastoma, Wilms Tumor, hepatic tumors, and germ cell tumors. Patients must have at least one lesion in areas accessible to HIFU.

Medgadget: This Phase I trial focuses on children and young adults with difficult to treat tumors. Given the potential side-effects of chemotherapy, should enhanced tumor targeting technologies that can reduce off-target effects be used more commonly, and not just for patients with recurrent or refractory tumors? Do you think these kinds of technologies will become more common in the future?

AeRang Kim: Yes for both of these questions. It is my belief that the only way we can advance therapy for pediatric cancers is to develop treatments that are more specific with less side effects. I do believe that these types of technologies for more targeted precision medicine are becoming more common now and this will continue in the future. If this treatment is tolerated and we find a safe dose, we hope we can incorporate promising therapies such as LTLD and HIFU into upfront treatment protocols.

 

Medgadget: Previous clinical trials with ThermoDox have employed radiofrequency ablation as the source of heat to trigger drug release at the tumor site. Have there been any trials using the MR-HIFU technology? How does it compare with radiofrequency ablation as an effective trigger for ThermoDox?

AeRang Kim: There is a Phase I adult study evaluating ultrasound guided focused ultrasound in patients with liver cancer. The study is too early to have reported any results. The principles of heat application would be hypothesized to be the same, but the advantages of HIFU as a heating method over radiofrequency ablation (RFA) are that it is completely non-invasive (no RFA needle); it allows for ablation of large volumes; there is no ionizing radiation used for guidance, and other heating modalities such as hyperthermia can be used.

 

Medgadget: Previous clinical trials of ThermoDox in conjunction with radiofrequency ablation have met with mixed results, with the best results coming when radiofrequency ablation was applied in an optimal manner. Will this influence the way that treatment is applied in this new trial?

AeRang Kim: What is fantastic about MR-HIFU is that we can actually quantify in real time the temperature of heating and the duration of heat so that we can provide optimal heating in conjunction with LTLD.

 

Medgadget: Does the HIFU treatment result in localized destruction of the tumor tissue, through the heating effect, or does the major therapeutic effect come from the action of the released doxorubicin?

AeRang Kim: MR-HIFU ablative therapy will result in localized destruction of tumor tissue through heating effect, but when combined with LTLD the doxorubicin will be released in the heated tumor margins and in any areas within the tumor that were not completely ablated, thus increasing the likelihood of complete tumor necrosis and hopefully minimize the possibility of tumor recurrence.

 

The ThermoDox concept, as applied to a variety of cancers, is illustrated in the following video:

Link: ThermoDox info page…

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New Embolization Agent Overcomes Limitations of Existing Methods

New Embolization Agent Overcomes Limitations of Existing Methods

 

embolization-material

 

Researchers from Harvard’s Wyss Institute, Brigham and Women’s Hospital, Mayo Clinic, and MIT have developed a new embolization material that may overcome the limitations of coils and existing liquid embolic agents. The hydrogel material changes its state between liquid and solid in response to physical pressure applied to it. It can be delivered via a catheter directly to a target vessel to completely block any blood from passing through. Unlike with coils, it does not require blood’s own coagulation properties to make it work, making it effective in patients on systemic blood thinners, and unlike existing liquid embolic agents the new material is much easier to control and to place so as not to affect other tissues or nearby stents. Eventually the material biodegrades and is replaced by the body’s own cells.

The material consists of gelatin molecules with tiny discs of silicate nanoplatelets mixed. The nanoplatelets solidify when under little pressure and liquefy when under a lot of it. This property allows it to be squeezed from a syringe as a liquid and to then solidify once it enters a vessel. This was tested by pushing the hydrogel material through existing catheters and analyzed how it can be used to embolize tortuous vessels.

embolized-vessel

The researchers also applied the material in mice and pigs, demonstrating that the new material was effective at completely occluding large vessels and then biodegrading to be replaced by natural tissue.

The researchers point out that the hydrogel can also be impegnated with contrast agents to be able to see its exact location under live fluoroscopy, which should aid surgeons immensely during embolization procedures.

Here’s a link to a video showing the action of the new biomaterial…

Study in Science Translational MedicineAn injectable shear-thinning biomaterial for endovascular embolization…

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Blood-Monitoring Disposable Smart Patch Delivers Blood Thinners On-Demand

Blood-Monitoring Disposable Smart Patch Delivers Blood Thinners On-Demand

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Thrombosis, the occlusion of vasculature by blood clots, is a precursor to debilitating conditions including stroke, pulmonary embolism, and heart attack. Blood thinners such as heparin or Coumadin are used to treat thrombosis, but necessitate ongoing blood tests for precise drug dosing. Researchers from the University of North Carolina at Chapel Hill and North Carolina State University have developed and tested a self-regulating drug eluting patch that monitors the level of thrombin (a clot initiating enzyme) in the blood, and releases appropriate amounts of heparin in response.

image descriptionThe microneedle patch is meant to stick to the skin and its polymer tips are impregnated with heparin molecules attached to hyaluronic acid via amino acid chains. Thrombin eats at the amino acid connections between the hyaluronic acid and heparin, releasing the drug. The amount of heparin released is proportional to the quantity of thrombin that passes by the microneedles, allowing the patch to be automatically responsive to any developing clots. Because the amount of heparin can be adjusted on the patch to the needs of each patient, the patch can also be personalized during manufacturing.

The smart patch was tested in a murine model and demonstrated superior efficacy at mitigating thrombosis compared to the conventional delivery of heparin via injection.  The current study provides compelling proof of principle, with additional preclinical testing on the horizon.

Study in journal Advanced MaterialsThrombin-Responsive Transcutaneous Patch for Auto-Anticoagulant Regulation…

Via: North Carolina State…

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Nanochip Mimics Nose Function and Sniffs Out Explosives

Nanochip Mimics Nose Function and Sniffs Out Explosives

Nanochip Mimics Nose Function and Sniffs Out Explosives

The dominant physical transport processes are analyzed in a free-surface microfluidic and surface-enhanced Raman spectroscopy (SERS) chemical detection system. The analysis describes the characteristic fluid dynamics and mass transport effects occurring in a microfluidic detection system whose analyte absorption and concentration capability is designed to operate on principles inspired by canine olfaction. The detection system provides continuous, real-time monitoring of particular vapor-phase analytes at concentrations of 1 ppb. The system is designed with a large free-surface-to-volume ratio microfluidic channel which allows for polar or hydrophilic airborne analytes to readily be partitioned from the surrounding gas phase into the aqueous phase for detection. The microfluidic stream can concentrate certain molecules by up to 6 orders of magnitude, and SERS can enhance the Raman signal by 9–10 orders of magnitude for molecules residing in the so-called SERS “hot spots”, providing extremely high detection sensitivity. The resulting vibrational spectra are sufficiently specific to identify the detected analyte unambiguously. Detection performance was demonstrated using a nominal 1 ppb, 2,4-dinitrotoluene (2,4-DNT) vapor stream entrained within N2 gas. Applications to homeland security arise from the system’s high sensitivity and its ability to provide highly reproducible, continuous chemical detection monitoring with minimal sampling requirements.

(Santa Barbara, CA —) Portable, accurate, and highly sensitive devices that sniff out vapors from explosives and other substances could become as commonplace as smoke detectors in public places, thanks to researchers at University of California, Santa Barbara.

Researchers at UCSB, led by professors Carl Meinhart of mechanical engineering and Martin Moskovits of chemistry, have designed a detector that uses microfluidic nanotechnology to mimic the biological mechanism behind canine scent receptors. The device is both highly sensitive to trace amounts of certain vapor molecules, and able to tell a specific substance apart from similar molecules.

“Dogs are still the gold standard for scent detection of explosives. But like a person, a dog can have a good day or a bad day, get tired or distracted,” said Meinhart. “We have developed a device with the same or better sensitivity as a dog’s nose that feeds into a computer to report exactly what kind of molecule it’s detecting.” The key to their technology, explained Meinhart, is in the merging of principles from mechanical engineering and chemistry in a collaboration made possible by UCSB’s Institute for Collaborative Biotechnologies .

Nanotech Device Mimics Dog’s Nose to Detect Explosives on Vimeo.

Results published this month in Analytical Chemistry show that their device can detect airborne molecules of a chemical called 2,4-dinitrotoluene, the primary vapor emanating from TNT-based explosives. The human nose cannot detect such minute amounts of a substance, but “sniffer” dogs have long been used to track these types of molecules. Their technology is inspired by the biological design and microscale size of the canine olfactory mucus layer, which absorbs and then concentrates airborne molecules.

“The device is capable of real-time detection and identification of certain types of molecules at concentrations of 1 ppb or below. Its specificity and sensitivity are unparalleled,” said Dr. Brian Piorek, former mechanical engineering doctoral student in Meinhart’s laboratory and Chief Scientist at Santa Barbara-based SpectraFluidics, Inc . The technology has been patented and exclusively licensed to SpectraFluidics, a company that Piorek co-founded in 2008 with private investors.

“Our research project not only brings different disciplines together to develop something new, but it also creates jobs for the local community and hopefully benefits society in general,” commented Meinhart.

Packaged on a fingerprint-sized silicon microchip and fabricated at UCSB’s state-of-the-art cleanroom facility, the underlying technology combines free-surface microfluidics and surface-enhanced Raman spectroscopy (SERS) to capture and identify molecules. A microscale channel of liquid absorbs and concentrates the molecules by up to six orders of magnitude. Once the vapor molecules are absorbed into the microchannel, they interact with nanoparticles that amplify their spectral signature when excited by laser light. A computer database of spectral signatures identifies what kind of molecule has been captured.

“The device consists of two parts,” explained Moskovits. “There’s a microchannel, which is like a tiny river that we use to trap the molecules and present them to the other part, a mini spectrometer powered by a laser that detects them. These microchannels are twenty times smaller than the thickness of a human hair.”

“The technology could be used to detect a very wide variety of molecules,” said Meinhart. “The applications could extend to certain disease diagnosis or narcotics detection, to name a few.”

Moskovits added, “The paper we published focused on explosives, but it doesn’t have to be explosives. It could detect molecules from someone’s breath that may indicate disease, for example, or food that has spoiled.”

The fundamental research was developed through an interdisciplinary collaboration between Professors Meinhart and Moskovits, and carried out by former doctoral researchers Dr. Piorek and Dr. Seung-Joon Lee. Their project was funded in part by UCSB’s Institute for Collaborative Biotechnologies through the Army Research Office and DARPA.

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The College of Engineering at University of California, Santa Barbara is recognized globally as a leader among the top tier of engineering education and research programs, and is renowned for a successful interdisciplinary approach to engineering research.

The Institute for Collaborative Biotechnologies at University of California, Santa Barbara is a uniquely interdisciplinary alliance of more than 150 researchers in academia, industry, and the U.S. Army that conducts unclassified, fundamental bio-inspired research in sensors, materials, biodiscovery, network science, and cognitive neuroscience. Led by the University of California, Santa Barbara, in collaboration with MIT, Caltech, the Army, and industry partners, the ICB transforms biological inspiration into technological innovation.

Why do we still use dogs to sniff out dangerous explosives at the airport? That’s because even with all the modern science and technology available, man’s best friend continues to be the best at it. Things may change, as researchers at the University of California in Santa Barbara have now developed a device that may rival a dog’s olfactory ability. Their nanotech device is inspired by the biology of canine scent receptors. It uses microfluidics to detect airborne molecules of TNT explosives and distinguish them from similar molecules. The results of the research were published in Analytical Chemistry.

A dog’s nose is more sensitive than a human nose and can pick up the scent of explosives very well. A dog however, is an animal, and the sensitivity of its nose can be disturbed by fatigue or distraction. This is a characteristic that computers and devices don’t share with living beings. That is what brought Carl Meinhart and Martin Moskovits to the idea of developing a device that is as sensitive as a dog’s nose in picking up TNT vapors.

From UCSB:

Packaged on a fingerprint-sized silicon microchip and fabricated at UCSB’s state-of-the-art cleanroom facility, the underlying technology combines free-surface microfluidics and surface-enhanced Raman spectroscopy (SERS) to capture and identify molecules. A microscale channel of liquid absorbs and concentrates the molecules by up to six orders of magnitude. Once the vapor molecules are absorbed into the microchannel, they interact with nanoparticles that amplify their spectral signature when excited by laser light. A computer database of spectral signatures identifies what kind of molecule has been captured.

Source : http://pubs.acs.org/doi/abs/10.1021/ac302497y?journalCode=ancham

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Photo Contest Profiles Role of Science in Modern Life

Photo Contest Profiles Role of Science in Modern Life

Photo Contest Profiles Role of Science in Modern Life

Rupert Hitchcox’s photo and story about his stuggle with hydrocephalus were chosen by a panel of judges to win first prize. Anne Hird, whose story and photo detailed how limited sight affects her and her husband’s life, and Andreas Sakka, whose story and photo showed how science helped his prematurely born son, tied as runners up. Thank-you for all of the entries!

To see a collection of photos and stories entered into the Living Science competition, please see the archive.

Rupert Hitchcox’s photo and story about his stuggle with hydrocephalus were chosen by a panel of judges to win first prize. Anne Hird, whose story and photo detailed how limited sight affects her and her husband’s life, and Andreas Sakka, whose story and photo showed how science helped his prematurely born son, tied as runners up. Thank-you for all of the entries!

To see a collection of photos and stories entered into the Living Science competition, please see the archive.

UK’s Department for Business, Innovation and Skills just ran a photo contest on their Science So What website to highlight the role that medical technology plays in people’s lives. The winner of the Living Science Competition, pictured above, is Rupert Hitchcox’s photo of life with hydrocephalus.

Source : http://tna.europarchive.org/20100630051843/http://sciencesowhat.direct.gov.uk/articles/health-and-society/people/the-living-science-competition-winners-announced

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DNA Sequencing Technology from Oxford Nanopore

DNA Sequencing Technology from Oxford Nanopore

DNA Sequencing Technology from Oxford Nanopore

Michael Berger at the Nanowerk blog has an article on the latest efforts to use nanopores to characterize proteins and sequence single DNA molecules. His report focuses on successful experiments that demonstrated the feasibility of single-molecule DNA through-the-pore spectroscopy. On our pages, we wrote on a number of promising experiments in which scientists developed special nanopore channels, that interacted with translocating molecules and “reported” their molecular structure and sequence (see flashbacks below).

From the current Nanowerk article:

“In recent years, the creation of nanochannels or nanopores in thin membranes has attracted much interest due to the potential to isolate and sense single DNA molecules while they translocate through the highly confined channels” Dr. Joshua Edel, a lecturer in micro- and nanotechnology at the Imperial College London, explains to Nanowerk. “Nanopores for such applications have already been fabricated but in all studies to date, the detection of translocation events is performed electrically by measuring the ionic current” (what this means is that molecules translocating through a nanopore will momentarily perturb the ionic current, with the duration of the perturbation and the magnitude of the current blockade providing more detailed information about molecular shape and structure).

Edel’s group, together with collaborators from Drexel University, recently presented proof-of-concept studies that describe a novel approach for optically detecting DNA translocation events through an array of solid-state nanopores which allows for ultrahigh-throughput, parallel detection at the single-molecule level (“Single-Molecule Spectroscopy Using Nanoporous Membranes”).

Oxford Nanopore Technologies Ltd, a privately held company that is developing a disruptive technology for the real-time electronic analysis of single molecules, today announced that it has raised £31.4 million ($50.8 million) in new funding via a private placement of ordinary shares in the Company.

“This round of funding, nearly all of which comes from existing investors, will support a range of corporate development activities including the development of our commercial infrastructure, expansion of our manufacturing function and further R&D for our DNA/RNA sequencing and protein/miRNA analysis applications. We will also continue to maintain our leadership position in nanopore innovation through maintenance and expansion of our broad intellectual property portfolio,” said Dr Gordon Sanghera, CEO of Oxford Nanopore.

-ends-

Note: The placement of ordinary shares in the Company under this fundraising does not constitute an offer of the Company’s shares to the public. No shares in the Company will be offered or sold to any person except in circumstances which have not resulted and will not result in an offer to the public.

Oxford Nanopore Technologies

Oxford Nanopore Technologies Ltd is developing a novel technology for direct, electronic detection and analysis of single molecules using nanopores. The modular, scalable GridION technology platform and miniaturised MinION instrument are designed to offer substantial benefits in a variety of applications.

The Company’s lead application is DNA sequencing which combines a nanopore with a processive enzyme for the analysis of DNA. Oxford Nanopore is also developing a Protein Analysis application that combines target proteins, aptamers and nanopores for direct, electronic analyses of those target proteins. These nanopore sensing techniques are combined with the Company’s proprietary electronics-based GridION and MinION systems. The Company also has collaborations for the development of solid-state nanopores.

Oxford Nanopore has collaborations and exclusive licensing deals with leading institutions including the University of Oxford, Harvard and UCSC. The Company has funding programmes in these laboratories to support the science of nanopore sensing. Oxford Nanopore has licensed or owns more than 350 patents and patent applications that relate to many aspects of nanopore sensing from protein nanopores to solid state nanopores and for the analysis of DNA, proteins and other molecules. This includes the use of functionalised solid-state nanopores for molecular characterisation, methods of fabricating solid-state nanopores and modifications of solid-state nanopores to adjust sensitivity or other parameters.

This transaction brings the total funds raised since the Company’s foundation in 2005 to £105.4 million.

Oxford Nanopore, formerly UK’s Oxford NanoLabs, has licensed nanopore technology from Harvard to help advance the company’s sequencing methods for DNAs and other molecules. This is not the first time we are reporting about the efforts to commercialize nanopore channels as DNA sequencing sites, since scientists have known for a while now about the ability of these channels to interact with translocating molecules, and “report” their molecular structure. (Check out the flashbacks below for previous posts on nanopore-assisted single molecule sequencing research.)

nanopore DNA Sequencing Technology from Oxford NanoporeFrom the press release by Oxford Nanopore:

Under the terms of this agreement with Harvard, Oxford Nanopore has exclusive rights to develop and commercialise a number of nanopore technological breakthroughs developed in the laboratories of three investigators at Harvard and their collaborators at the University of California Santa Cruz (UCSC) and the National Institute of Standards and Technology (NIST), an agency of the US Department of Commerce. The investigators include: Professors Daniel Branton, George Church and Jene Golovchenko at Harvard; David Deamer and Mark Akeson at UCSC and John Kasianowicz at NIST.

These academics have pioneered the research of DNA translocation through nanopores and the potential for DNA sequencing using this method. This is complementary to the work of Professor Hagan Bayley, the founder of Oxford Nanopore Technologies. Professor Bayley pioneered the field of nanopores as sensors of single molecules, with a specific focus on the identification of DNA bases.

From the company’s technology page:

The nanopore sequencing method under development at Oxford Nanopore Technologies, BASE™ technology, is label-free and measures single DNA bases directly. The method does not rely on amplification or labelling, and provides a direct electrical signal for base calling. Whilst the evolution of other technologies relies on improvements in existing chemical, optical or bioinformatics procedures, nanopores would bypass these to deliver a genuinely revolutionary sequencing method.

43634poi DNA Sequencing Technology from Oxford NanoporeThe natural ?-hemolysin nanopore alone is not capable of DNA sequencing. Oxford Nanopore is using protein engineering techniques to adapt the nanopore for the detection of DNA bases.

A key achievement in adapting the nanopore has been the covalent attachment of a cyclodextrin molecule to the inside surface of the nanopore, This acts as a binding site for individual DNA bases and allows accurate measurement of their passage through the nanopore binding site.

Furthermore, Oxford Nanopore is addressing the issue of how DNA is passed through the nanopore by adopting a novel exonuclease sequencing approach. This takes advantage of the ability of exonuclease enzymes to process DNA and cleave individual bases from the end of a DNA strand. By positioning an exonuclease in the correct position on a nanopore, the enzyme can potentially deliver individual DNA bases in sequence into the nanopore for rapid and accurate identification.

Source : http://www.nanoporetech.com/news/press-releases/view/40

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Nanotubes and Stem Cells Combine for Cardiac Tissue Repair

Nanotubes and Stem Cells Combine for Cardiac Tissue Repair

Nanotubes and Stem Cells Combine for Cardiac Tissue Repair

Nanotechnology based stem cell therapies for damaged heart muscles

(Nanowerk Spotlight) Regenerative medicine is an area in which stem cells hold great promise for overcoming the challenge of limited cell sources for tissue repair. Stem cell research is being pursued vigorously in laboratories all over the world (except in the U.S., where federal funding for embryonic stem cell research has been severely restricted by the current administration) in the hope of achieving major medical breakthroughs. Scientists are striving to create therapies that rebuild or replace damaged cells with tissues grown from stem cells and offer hope to people suffering from cancer, diabetes, cardiovascular disease, spinal-cord injuries, and many other disorders.

Embryonic stem cells are pluripotent. That means that during normal embryogenesis – the process by which the embryo is formed and develops – human embryonic stem cells can differentiate into all derivatives of the three primary germ layers: ectoderm, endoderm, and mesoderm. Researchers have also found undifferentiated cells – adult stem cells – in children and adults. Unlike embryonic stem cells, the use of adult stem cells in research and therapy is not controversial because the production of adult stem cells does not require the creation or destruction of an embryo.

Often, adult stem cells are not pluripotent but multipotent. That means they can differentiate only into a limited variety of cell type. One such example are mesenchymal stem cells (MSC) – adult stems cells found in bone marrow which can be differentiated into bone, cartilage, fat, and connective tissues – which offer tremendous potential for the repair and or regeneration of damaged tissues and organs.

An area of particular interest is differentiation of MSC into cardiomyocytes (let’s simply call them ‘heart muscle cells’) for damaged heart muscle tissue. In a heart attack, part of the heart muscle loses its blood supply and cells in that part of the heart die, thereby damaging the muscle. This reduces the ability of the heart to pump blood around the body. Considering that coronary heart disease is the leading cause of death in most Western countries (in America with almost half a million fatalities and well over 1 million new and recurrent coronary attacks), stem cell therapy – to repair heart muscle cells, and restore the viability and function of the area already damaged – could have a tremendous impact on modern medicine.

“Recently, carbon nanotubes (CNTs) have been generating great excitement in the fields of bioengineering and drug delivery research – however, very little is known about the affect of CNTs on MSC response” Dr. Valerie Barron tells Nanowerk. “Therefore, the main aim of one of our recent research studies was to investigate the effect of CNTs on human MSC (hMSC) biocompatibility, proliferation and multipotency.”

In this study, Barron, a Senior Researcher at the National Centre for Biomedical Engineering Science at National University of Ireland (NUI), together with collaborators from NUI’s Regenerative Medicine Institute and Department of Anatomy, investigated a range of different types of CNTs,including single-walled nanotubes (SWCNTs), multi-walled nanotubes (MWCNTs) and functionalized CNTs.

Reporting their findings in the July 12, 2008 online edition of Nano Letters, (“Carbon Nanotubes and Mesenchymal Stem Cells: Biocompatibility, Proliferation and Differentiation”), first-authored by Barron’s colleague Emma Mooney, the NUI, Galway scientists revealed that at low concentrations of COOH-functionalized SWCNTs, the CNTs had no significant effect on cell viability or proliferation. In addition, by fluorescently labeling the COOH functionalized SWCNTs, the CNTs were seen to migrate to a nuclear location within the cell after 24h, without adversely affecting the cellular ultrastructure. Moreover, the CNT had no affect on adipogenesis, chondrogenesis or osteogenesis.

Uptake of COOH-functionalized single-walled carbon nanotubes by the cell

Uptake of COOH-functionalized SWCNT by the cell. Fluorescent images of biotinylated CNT within the cell after (a) 24 h, (b) 48 h, and (c) 6 days and (d) hMSC alone (scale bar 130 µm). (Reprinted with permission from American Chemical Society)

Previous research has shown that CNTs migrate into cancer cells and therefore can be used for biomolecule delivery directly into the cells. This is the first study to examine the effect of CNTs on hMSC and as such is important for new and emerging technologies in drug delivery, tissue engineering, and regenerative medicine. At low concentrations, CNTs have minimal affect on MSC viability and multipotency. Therefore, they have great potential to advance the field in a number of ways including

Manipulation of MSC differentiation pathways;

Development of nanovehicles for delivering biomolecule-based cargos to mesenchymal stem cells;

Creation of novel biomedical applications for electroactive carbon nanotubes in combination with mesenchymal stem cells.”

In a previous position at Trinity College Dublin, Barron had worked in Werner Blau’s Molecular Electronics and Nanotechnology group where she gained a tremendous appreciation for carbon nanotubes. “As a biomaterials scientist, I could see their potential in biomedical applications” she says. At NUI, Galway she therefore teamed up with Murphy to examine the effect of CNTs on MSC differentiation. Both researchers were aware of the fact that, since there is no clinical therapy available for the repair of damaged heart muscle, there exist tremendous opportunities for the creation of novel nanotechnology based therapies.

Since carbon nanotubes are electrically conductive, there is a huge potential for the manipulation of MSC differentiation pathways to create electroactive cells such as those found in the heart. In particular, specific applications could result in novel MSC based cell therapies for electroactive tissue repair; novel biomolecule delivery vehicle for manipulation of MSC differentiation pathways; and electroactive CNT scaffolds for damaged electroactive tissues.

“At present, we are developing a novel electrophysiological environment to promote MSC differentiation towards a cardiomyocyte lineage” says Barron. “In the short-term we plan to focus on optimizing this approach to develop nanotechnology based cell therapies. In the longer term we hope to use the nanotubes as delivery vehicles for a range of different biomolecules for the manipulation of MSC differentiation pathways towards a range of different cell types.

Nanowerk is spotlighting research being conducted to study the viability of using stem cells and carbon nanotubes to repair damaged heart tissue.

From Michael Berger at Nanowerk:

An area of particular interest is differentiation of MSC [mesenchymal stem cells] into cardiomyocytes (let’s simply call them ‘heart muscle cells’) for damaged heart muscle tissue. In a heart attack, part of the heart muscle loses its blood supply and cells in that part of the heart die, thereby damaging the muscle. This reduces the ability of the heart to pump blood around the body. Considering that coronary heart disease is the leading cause of death in most Western countries (in America with almost half a million fatalities and well over 1 million new and recurrent coronary attacks), stem cell therapy – to repair heart muscle cells, and restore the viability and function of the area already damaged – could have a tremendous impact on modern medicine.

“Recently, carbon nanotubes (CNTs) have been generating great excitement in the fields of bioengineering and drug delivery research – however, very little is known about the affect of CNTs on MSC response” Dr. Valerie Barron tells Nanowerk. “Therefore, the main aim of one of our recent research studies was to investigate the effect of CNTs on human MSC (hMSC) biocompatibility, proliferation and multipotency.”

In this study, Barron, a Senior Researcher at the National Centre for Biomedical Engineering Science at National University of Ireland (NUI), together with collaborators from NUI’s Regenerative Medicine Institute and Department of Anatomy, investigated a range of different types of CNTs,including single-walled nanotubes (SWCNTs), multi-walled nanotubes (MWCNTs) and functionalized CNTs.

Source : http://www.nanowerk.com/spotlight/spotid=6883.php

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Harvard Scientists Bend Nanowires 2-D, 3-D

Harvard Scientists Bend Nanowires 2-D, 3-D

Harvard Scientists Bend Nanowires 2-D, 3-D

Taking nanomaterials to a new level of structural complexity, scientists have determined how to introduce kinks into arrow-straight nanowires, transforming them into zigzagging two- and three-dimensional structures with correspondingly advanced functions.

Taking nanomaterials to a new level of structural complexity, scientists have determined how to introduce kinks into arrow-straight nanowires, transforming them into zigzagging two- and three-dimensional structures with correspondingly advanced functions.

The work is described this week in the journal Nature Nanotechnology by Harvard University researchers, led by Bozhi Tian and Charles M. Lieber.

Among possible applications, the authors say, the new technology could foster a new nanoscale approach to detecting electrical currents in cells and tissues.

“We are very excited about the prospects this research opens up for nanotechnology,” said Lieber, Mark Hyman Jr. Professor of Chemistry in Harvard’s Faculty of Arts and Sciences. “For example, our nanostructures make possible integration of active devices in nanoelectronic and photonic circuits, as well as totally new approaches for extra- and intracellular biological sensors. This latter area is one where we already have exciting new results, and one we believe can change the way much electrical recording in biology and medicine is carried out.”

Lieber and Tian’s approach involves the controlled introduction of triangular “stereocenters” – essentially, fixed 120-degree joints – into nanowires, structures that have previously been rigidly linear. These stereocenters, analogous to the chemical hubs found in many complex organic molecules, introduce kinks into 1-D nanostructures, transforming them into more complex forms.

The researchers were able to introduce stereocenters as nanowires, which are self-assembled. The researchers halted growth of the 1-D nanostructures for 15 seconds by removing key gaseous reactants from the chemical brew in which the process was taking place, replacing these reactants after joints had been introduced into the nanostructures. This approach resulted in a 40 percent yield of bent nanowires, which can then be purified to achieve higher yields.

“The stereocenters appear as kinks, and the distance between kinks is completely controlled,” said Tian, a research assistant in Harvard’s Department of Chemistry and Chemical Biology. “Moreover, we demonstrated the generality of our approach through synthesis of 2-D silicon, germanium, and cadmium sulfide nanowire structures.”

The research by Lieber and Tian is the latest in the years-long efforts by scientists to control the composition and structure of nanowires during synthesis. Despite advances in these areas, the ability to control the design and growth of self-assembling nanostructures has been limited. Lieber and Tian’s work takes the formation of 2-D nanostructures a step further by enabling the introduction of electronic devices at the stereocenters.

“An important concept that emerged from these studies is that of introducing functionality at defined nanoscale points for the first time – in other words, nanodevices that can ‘self-label,’ ” Lieber said. “We illustrated this novel capability by the insertion of p–n diodes and field-effect transistors precisely at the stereocenters.”

Such self-labeled structures could open up the possibility of introducing nanoelectronics, photodetectors, or biological sensors into complex nanoscale structures.

Lieber and Tian’s co-authors are Ping Xie and Thomas J. Kempa of Harvard’s Department of Chemistry and Chemical Biology and David C. Bell of Harvard’s Center for Nanoscale Systems. Their work was funded by the National Institutes of Health, the McKnight Foundation, the MITRE Corp., and the National Science Foundation.

The ability to control and modulate the composition1, 2, 3, 4, doping1, 3, 4, 5, crystal structure6, 7, 8 and morphology9, 10 of semiconductor nanowires during the synthesis process has allowed researchers to explore various applications of nanowires11, 12, 13, 14, 15. However, despite advances in nanowire synthesis, progress towards the ab initio design and growth of hierarchical nanostructures has been limited. Here, we demonstrate a ‘nanotectonic’ approach that provides iterative control over the nucleation and growth of nanowires, and use it to grow kinked or zigzag nanowires in which the straight sections are separated by triangular joints. Moreover, the lengths of the straight sections can be controlled and the growth direction remains coherent along the nanowire. We also grow dopant-modulated structures in which specific device functions, including p–n diodes and field-effect transistors, can be precisely localized at the kinked junctions in the nanowires.

Harvard Gazette is reporting that the university’s nanotechnologists developed a new methodology to produce 2-D and 3-D shaped nanowires by introducing bends through a series of stereocenters:

“We are very excited about the prospects this research opens up for nanotechnology,” said Lieber, Mark Hyman Jr. Professor of Chemistry in Harvard’s Faculty of Arts and Sciences. “For example, our nanostructures make possible integration of active devices in nanoelectronic and photonic circuits, as well as totally new approaches for extra- and intracellular biological sensors. This latter area is one where we already have exciting new results, and one we believe can change the way much electrical recording in biology and medicine is carried out.”

Lieber and Tian’s approach involves the controlled introduction of triangular “stereocenters” – essentially, fixed 120-degree joints – into nanowires, structures that have previously been rigidly linear. These stereocenters, analogous to the chemical hubs found in many complex organic molecules, introduce kinks into 1-D nanostructures, transforming them into more complex forms.

The researchers were able to introduce stereocenters as nanowires, which are self-assembled. The researchers halted growth of the 1-D nanostructures for 15 seconds by removing key gaseous reactants from the chemical brew in which the process was taking place, replacing these reactants after joints had been introduced into the nanostructures. This approach resulted in a 40 percent yield of bent nanowires, which can then be purified to achieve higher yields.

“The stereocenters appear as kinks, and the distance between kinks is completely controlled,” said Tian, a research assistant in Harvard’s Department of Chemistry and Chemical Biology. “Moreover, we demonstrated the generality of our approach through synthesis of 2-D silicon, germanium, and cadmium sulfide nanowire structures.”

The research by Lieber and Tian is the latest in the years-long efforts by scientists to control the composition and structure of nanowires during synthesis. Despite advances in these areas, the ability to control the design and growth of self-assembling nanostructures has been limited. Lieber and Tian’s work takes the formation of 2-D nanostructures a step further by enabling the introduction of electronic devices at the stereocenters.

“An important concept that emerged from these studies is that of introducing functionality at defined nanoscale points for the first time – in other words, nanodevices that can ‘self-label,’ ” Lieber said. “We illustrated this novel capability by the insertion of p–n diodes and field-effect transistors precisely at the stereocenters.”

Such self-labeled structures could open up the possibility of introducing nanoelectronics, photodetectors, or biological sensors into complex nanoscale structures.

Source : http://news.harvard.edu/gazette/story/2009/10/nanowires-go-2-d-3-d/

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New polymer nanoparticles can generate heat and kill colorectal cancer cells

New polymer nanoparticles can generate heat and kill colorectal cancer cells

Researchers at Wake Forest Baptist Medical Center have modified electrically-conductive polymers, commonly used in solar energy applications, to develop revolutionary polymer nanoparticles (PNs) for a medical application. When the nanoparticles are exposed to infrared light, they generate heat that can be used to kill colorectal cancer cells.

The study was directed by Assistant Professor of Plastic and Reconstructive Surgery, Nicole H. Levi-Polyachenko, Ph.D., and done in collaboration with colleagues at the Center for Nanotechnology and Molecular Materials at Wake Forest University. This study was recently published online, ahead of print, in the journal, Macromolecular Bioscience (DOI: 10.1002/mabi.201200241).

Levi-Polyachenko and her team discovered a novel formulation that gives the polymers two important capabilities for medical applications: the polymers can be made into nanoparticles that are easily dispersed in water and generate a lot of heat when exposed to infrared light.

Results of this study showed that when colorectal cancer cells incubated with the PNs were exposed to five minutes of infrared light, the treatment killed up to 95 percent of cells. “The results of this study demonstrate how new medical advancements are being developed from materials science research,” said Levi-Polyachenko.

The team made polymer nanoparticles and showed that they could undergo repeated cycles of heating and cooling without affecting their heating ability. This offers advantages over metal nanoparticles, which can melt during photothermal treatments, leading to a loss of heating efficiency. This also allows for subsequent treatments to target cells that are resistant to heat-induced killing.

A challenge with other electrically-conductive polymers that have recently been explored for photothermal therapy is that these other polymers absorb across a wide range of infrared light. Christopher M. MacNeill, Ph.D., post-doctoral researcher at Wake Forest and first author on the paper, noted that, “we have specifically used electrically-conductive polymers designed to absorb a very narrow region of infrared light, and have also developed small, 50-65nm, polymer nanoparticles in order to optimize both biological transport as well as heat transfer.” For example, 50nm is about 2000 times smaller than a human hair.

In addition, the new PNs are organic and did not show any evidence of toxicity, alleviating concerns about the effect of nanoparticles that may potentially linger in the body.

“There is a lot more research that needs to be done so that these new nanoparticles can be used safely in patients,” Levi-Polyachenko cautioned, “but the field of electrically-conductive polymers is broad and offers many opportunities to develop safe, organic nanoparticles for generating heat locally in a tissue. We are very enthusiastic about future medical applications using these new nanoparticles, including an alternative approach for treating colorectal cancer.”

Source : http://www.news-medical.net/news/20121121/New-polymer-nanoparticles-can-generate-heat-and-kill-colorectal-cancer-cells.aspx

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Mesoporous Silica Nanoparticles Improve Delivery of Hydrophobic Anticancer Drugs

Mesoporous Silica Nanoparticles Improve Delivery of Hydrophobic Anticancer Drugs

Mesoporous Silica Nanoparticles Improve Delivery of Hydrophobic Anticancer Drugs

Researchers at UCLA have successfully manipulated nanomaterials to create a new drug-delivery system that promises to solve the challenge of the poor water solubility of today’s most promising anticancer drugs and thereby increase their effectiveness.

The poor solubility of anticancer drugs is one of the major problems in cancer therapy because the drugs require the addition of solvents in order to be easily absorbed into cancer cells. Unfortunately, these solvents not only dilute the potency of the drugs but create toxicity as well.

In a paper scheduled to be published in the nanoscience journal Small in June, researchers from UCLA’s California NanoSystems Institute and Jonsson Cancer Center report a novel approach using silica-based nanoparticles to deliver the anticancer drug camptothecin and other water-insoluble drugs into human cancer cells.

The study is led by Fuyu Tamanoi, UCLA professor of microbiology, immunology and molecular genetics and director of the Jonsson Cancer Center’s Signal Transduction and Therapeutics Program Area, and Jeffrey Zink, UCLA professor of chemistry and biochemistry.

Tamanoi and Zink devised a method for incorporating the representative hydrophobic anticancer drug camptothecin into the pores of fluorescent mesoporous silica nanoparticles and delivering the particles into a variety of human cancer cells to induce cell death. The results suggest that the mesoporous silica nanoparticles might be used as a vehicle to overcome the insolubility problem of many anticancer drugs.

“Silica nanomaterials show promise for delivering camptothecin and other water-insoluble drugs,” Tamanoi said. “We have successfully loaded hydrophobic anticancer drugs into mesoporous nanoparticles and delivered them into human cancer cells to induce cell death.”

“The beauty of our findings is that these nanoparticles are biocompatible, contain tubular pores and are relatively easy to modify,” Zink said. “Additional modification by attaching a ligand against a cancer-cell-specific receptor can make the nanoparticles recognizable by cancer cells.”

A critical obstacle and challenge for cancer therapy is the limited availability of effective biocompatible delivery systems. Since many effective anticancer agents have poor water solubility, the development of novel delivery systems for these molecules without the use of organic solvents has received significant attention.

Camptothecin (CPT) and its derivatives are considered to be among the most effective anticancer drugs of the 21st century. Although studies have demonstrated their effectiveness against carcinomas of the stomach, colon, neck and bladder, as well as against breast cancer, small-cell lung cancer and leukemia in vitro, clinical application of CPT in humans has only been carried out with CPT derivatives that have improved water solubility.

“In order to be used on humans, current cancer therapies such as CPT or Taxol, which are poorly water soluble, must be mixed with organic solvents in order to be delivered into the body,” Tamanoi said. “These elements produce toxic side effects and in fact decrease the potency of the cancer therapy.”

To overcome these problems, drug delivery systems using pegylated polymers, liposomal particles or albumin-based nanoparticles have been developed.

The new research findings show that mesoporous silica nanoparticles offer great potential and a promising approach to the delivery of therapeutic agents into targeted organs or cells. The pores in the nanoparticles could be closed by constructing an appropriate cap structure. This provides the ability to control the release of anticancer drugs by external stimuli.

The research was supported by grants from the National Institutes of Health and the National Science Foundation and represents a collaboration between two totally different fields: bioscience and chemistry. The researchers came together because of their common interests in the identification of novel anticancer drugs and the potential for nano-delivery. Both Tamanoi and Zink are members of the California NanoSystems Institute at UCLA, which encourages cross-disciplinary collaboration to solve problems in nanoscience and nanotechnology.

For information about Fuyu Tamanoi’s research, visit the Tamanoi Research Lab’s Web site at www.mimg.ucla.edu/faculty/tamanoi.

For more information about Jeffrey Zink, visit the Zink Group Web site at www.chem.ucla.edu/dept/Faculty/zink/index.php.

About the California NanoSystems Institute

The California NanoSystems Institute (CNSI) is a multidisciplinary research center at UCLA whose mission is to encourage university-industry collaboration and to enable the rapid commercialization of discoveries in nanosystems. CNSI members include some of the world’s preeminent scientists, and the work conducted at the institute represents world-class expertise in five targeted areas of nanosystems-related research: renewable energy; environmental nanotechnology and nanotoxicology; nanobiotechnology and biomaterials; nanomechanical and nanofluidic systems; and nanoelectronics, photonics and architectonics. For additional information, visit the CNSI Web site at www.cnsi.ucla.edu.

About UCLA

UCLA is California’s largest university, with an enrollment of nearly 37,000 undergraduate and graduate students. The UCLA College of Letters and Science and the university’s 11 professional schools feature renowned faculty and offer more than 300 degree programs and majors. UCLA is a national and international leader in the breadth and quality of its academic, research, health care, cultural, continuing education and athletic programs. Four alumni and five faculty have been awarded the Nobel Prize.

Pacific Northwest National Laboratory is reporting that its scientists observed a reemergence of function in enzymes, thought to be expired, when these enzymes were placed in a material called functionalized mesoporous silica:

Inactive enzymes entombed in tiny honeycomb-shaped holes in silica can spring to life, scientists at the Department of Energy’s Pacific Northwest National Laboratory have found.

The discovery came when they decided to salvage enzymes that had been in a refrigerator long past their expiration date. Enzymes are proteins that are not actually alive but come from living cells and perform chemical conversions.

To the research team’s surprise, enzymes that should have fizzled months before perked right up when entrapped in a nanomaterial called functionalized mesoporous silica, or FMS. The result points the way for exploiting these enzyme traps in food processing, decontamination, biosensor design and any other pursuit that requires controlling catalysts and sustaining their activity.

“There’s a school of thought that the reason enzymes work better in cells than in solution is because the concentration of enzymes surrounded by other biomolecules in cells is about 1,000 to 10,000 time more than in standard biochemistry lab conditions,” said Eric Ackerman, PNNL chief scientist and senior author of a related study that appears today in the journal Nanotechnology. “This crowding is thought to stabilize and keep enzymes active.”

The silica-spun FMS pores, hexagons about 30 nanometers in diameter, mimic the crowding of cells. Ackerman, lead author Chenghong Lei and colleagues said crowding is important because it induces an unfolded, free-floating protein to refold; upon refolding, it reactivates and becomes capable of catalyzing thousands of reactions a second.

The FMS is made first, and the enzymes are added later. This is important, the authors said, because other schemes for entrapping enzymes usually incorporate the material and enzymes in one harsh mixture that can cripple enzyme function forever.

In this study, the authors reported having “functionalized” the silica pores by lining them with compounds that varied depending on the enzyme to be ensnared — amine and carboxyl groups carrying charges opposite that of three common, off-the-shelf biocatalysts: glucose oxidase (GOX), glucose isomerase (GI) and organophosphorus hydrolase (OPH).

Picture an enzyme in solution, floating unfolded like a mop head suspended in a water bucket. When that enzyme comes into contact with a pore, the protein is pulled into place by the oppositely charged FMS and squeezed into active shape inside the pore. So loaded, the pore is now open for business; substances in the solution that come into contact with the enzyme can now be catalyzed into the desired product. For example, GI turns glucose to fructose, and standard tests for enzyme activity confirmed that FMS-GI was as potent or better at making fructose as enzyme in solution. OPH activity doubled, while GOX activity varied from 30 percent to 160 percent, suggesting that the enzyme’s orientation in the pore is important.

We’ve certainly seen mesoporous silica before. Thought to have a range of important unique qualities for nanomedicine research (see our flashbacks below), this material has again demonstrated its potential usefulness in the latest study:

The poor solubility of anticancer drugs is one of the major problems in cancer therapy because the drugs require the addition of solvents in order to be easily absorbed into cancer cells. Unfortunately, these solvents not only dilute the potency of the drugs but create toxicity as well.

In a paper scheduled to be published in the nanoscience journal Small in June, researchers from UCLA’s California NanoSystems Institute and Jonsson Cancer Center report a novel approach using silica-based nanoparticles to deliver the anticancer drug camptothecin and other water-insoluble drugs into human cancer cells.

The study is led by Fuyu Tamanoi, UCLA professor of microbiology, immunology and molecular genetics and director of the Jonsson Cancer Center’s Signal Transduction and Therapeutics Program Area, and Jeffrey Zink, UCLA professor of chemistry and biochemistry.

Tamanoi and Zink devised a method for incorporating the representative hydrophobic anticancer drug camptothecin into the pores of fluorescent mesoporous silica nanoparticles and delivering the particles into a variety of human cancer cells to induce cell death. The results suggest that the mesoporous silica nanoparticles might be used as a vehicle to overcome the insolubility problem of many anticancer drugs.

“Silica nanomaterials show promise for delivering camptothecin and other water-insoluble drugs,” Tamanoi said. “We have successfully loaded hydrophobic anticancer drugs into mesoporous nanoparticles and delivered them into human cancer cells to induce cell death.”

“The beauty of our findings is that these nanoparticles are biocompatible, contain tubular pores and are relatively easy to modify,” Zink said. “Additional modification by attaching a ligand against a cancer-cell-specific receptor can make the nanoparticles recognizable by cancer cells.”

A critical obstacle and challenge for cancer therapy is the limited availability of effective biocompatible delivery systems. Since many effective anticancer agents have poor water solubility, the development of novel delivery systems for these molecules without the use of organic solvents has received significant attention.

Camptothecin (CPT) and its derivatives are considered to be among the most effective anticancer drugs of the 21st century. Although studies have demonstrated their effectiveness against carcinomas of the stomach, colon, neck and bladder, as well as against breast cancer, small-cell lung cancer and leukemia in vitro, clinical application of CPT in humans has only been carried out with CPT derivatives that have improved water solubility.

“In order to be used on humans, current cancer therapies such as CPT or Taxol, which are poorly water soluble, must be mixed with organic solvents in order to be delivered into the body,” Tamanoi said. “These elements produce toxic side effects and in fact decrease the potency of the cancer therapy.”

To overcome these problems, drug delivery systems using pegylated polymers, liposomal particles or albumin-based nanoparticles have been developed.

The new research findings show that mesoporous silica nanoparticles offer great potential and a promising approach to the delivery of therapeutic agents into targeted organs or cells. The pores in the nanoparticles could be closed by constructing an appropriate cap structure. This provides the ability to control the release of anticancer drugs by external stimuli.

Source : http://newsroom.ucla.edu/portal/ucla/Researchers-at-UCLA-Develop-New-8001.aspx?RelNum=8001

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