Chen Y.E.,Harvard University |
Tsao H.,Massachusetts General Hospital |
Tsao H.,Wellman Center for Photomedicine
Journal of the American Academy of Dermatology | Year: 2013
Complex communities of bacteria, fungi, and viruses thrive on our skin. The composition of these communities depends on skin characteristics, such as sebaceous gland concentration, moisture content, and temperature, as well as on host genetics and exogenous environmental factors. Recent metagenomic studies have uncovered a surprising diversity within these ecosystems and have fostered a new view of commensal organisms as playing a much larger role in immune modulation and epithelial health than previously expected. Understanding microbe-host interactions and discovering the factors that drive microbial colonization will help us understand the pathogenesis of skin diseases and develop new promicrobial and antimicrobial therapeutics. © 2012 by the American Academy of Dermatology, Inc.
Pache C.,Ecole Polytechnique Federale de Lausanne |
Bocchio N.L.,Ecole Polytechnique Federale de Lausanne |
Bouwens A.,Ecole Polytechnique Federale de Lausanne |
Villiger M.,Ecole Polytechnique Federale de Lausanne |
And 6 more authors.
Optics Express | Year: 2012
We introduce photothermal optical lock-in Optical Coherence Microscopy (poli-OCM), a volumetric imaging technique, which combines the depth sectioning of OCM with the high sensitivity of photothermal microscopy while maintaining the fast acquisition speed inherent to OCM. We report on the detection of single 40 nm gold particles with a 0.5 μm lateral and 2 μm axial resolution over a 50 μm depth of field and the three-dimensional localization of gold colloids within living cells. In combination with intrinsic sample contrast measured with dark-field OCM, poli-OCM offers a versatile platform for functional cell imaging. © 2012 Optical Society of America.
Agency: Department of Defense | Branch: Air Force | Program: STTR | Phase: Phase I | Award Amount: 99.98K | Year: 2007
Nearly 27,000 soldiers have been injured in the present conflicts in Iraq and Afghanistan. Advances in trauma treatments have allowed a greater percentage of these casualties to survive than previously; with the advent of excellent body armor more injuries are now seen in extremities than before, including nerve and blood vessel damage. A rapid repair of vascular injuries improves outcomes for injured soldiers, by decreasing the necessity of amputation. Photochemical Tissue Bonding is a technique that consists of a photo-active dye capable of crosslinking collagen at the site of injury when exposed to an intense light source. Developed by Drs. Redmond and Kochevar of the Wellman Laboratories of Photomedicine, the technique shows exceptional promise for complete vascular repair. A system comprising a stent and light source, which will address the requirements of rapid deployment in a forward field hospital and relative simplicity of use, is required to translate this technology from the clinic to the front line. Infoscitex Corporation (IST), in cooperation with Wellman Laboratories, proposes to develop a rapidly degradable and biologically compatible stent with the appropriate mechanical properties for use in this application. Additionally IST will explore design parameters and propose solutions for a portable isotropic light source.
Bioart ranges from bacterial manipulation to glowing rabbits, cellular sculptures, and—in the case of Australian-British artist Nina Sellars—documentation of an ear prosthetic that was implanted onto fellow artist Stelarc's arm. In the pursuit of creating art, practitioners have generated tools and techniques that have aided researchers, while sometimes crossing into controversy, such as by releasing invasive species into the environment, blurring the lines between art and modern biology, raising philosophical, societal, and environmental issues that challenge scientific thinking. "Most people don't know that bioart exists, but it can enable scientists to produce new ideas and give us opportunities to look differently at problems," says author Ali K. Yetisen, who works at Harvard Medical School and the Wellman Center for Photomedicine, Massachusetts General Hospital. "At the same time there's been a lot of ethical and safety concerns happening around bioart and artists who wanted to get involved in the past have made mistakes." In between experiments, Alexander Fleming would paint stick figures and landscapes on paper and in Petri dishes using bacteria. In 1928, after taking a brief hiatus from the lab, he noticed that portions of his "germ paintings," had been killed. The culprit was a fungus, penicillin—a discovery that would revolutionize medicine for decades to come. In 1938, photographer Edward Steichen used a chemical to genetically alter and produce interesting variations in flowering delphiniums. This chemical, colchicine, would later be used by horticulturalists to produce desirable mutations in crops and ornamental plants. In the late 18th and early 19th centuries, the arts and sciences moved away from traditionally shared interests and formed secular divisions that persisted well into the 20th century. "Appearance of environmental art in the 1970s brought about renewed awareness of special relationships between art and the natural world," Yetisen says. To demonstrate how we change landscapes, American sculptor Robert Smithsonian paved a hillside with asphalt, while Bulgarian artist Christo Javacheffa (of Christo and Jeanne-Claude) surrounded resurfaced barrier islands with bright pink plastic. These pieces could sometimes be destructive, however, such as in Ten Turtles Set Free by German-born Hans Haacke. To draw attention to the excesses of the pet trade, he released what he thought were endangered tortoises back to their natural habitat in France, but he inadvertently released the wrong subspecies, thus compromising the genetic lineages of the endangered tortoises as the two varieties began to mate. By the late 1900s, technological advances began to draw artists' attention to biology, and by the 2000s, it began to take shape as an artistic identity. Following Joe Davis' transgenic Microvenus came a miniaturized leather jacket made of skin cells, part of the Tissue Culture & Art Project (initiated in 1996) by duo Oran Catts and Ionat Zurr. Other examples of bioart include: the use of mutant cacti to simulate appearance of human hair in the place of cactus spines by Laura Cinti of University College London's C-Lab; modification of butterfly wings for artistic purposes by Marta de Menezes of Portugal; and photographs of amphibian deformation by American Brandon Ballengée. "Bioart encourages discussions about societal, philosophical, and environmental issues and can help enhance public understanding of advances in biotechnology and genetic engineering," says co-author Ahmet F. Coskun, who works in the Division of Chemistry and Chemical Engineering at California Institute of Technology. Today, Joe Davis is a research affiliate at MIT Biology and "Artist-Scientist" at the George Church Laboratory at Harvard—a place that fosters creativity and technological development around genetic engineering and synthetic biology. "It's Oz, pure and simple," Davis says. "The total amount of resources in this environment and the minds that are accessible, it's like I come to the city of Oz every day." But it's not a one-way street. "My particular lab depends on thinking outside the box and not dismissing things because they sound like science fiction," says Church, who is also part of the Wyss Institute for Biologically Inspired Engineering. "Joe is terrific at keeping us flexible and nimble in that regard." For example, Davis is working with several members of the Church lab to perform metagenomics analyses of the dust that accumulates at the bottom of money-counting machines. Another project involves genetically engineering silk worms to spin metallic gold—an homage to the fairy tale of Rumpelstiltskin. "I collaborate with many colleagues on projects that don't necessarily have direct scientific results, but they're excited to pursue these avenues of inquiry that they might not or would not look into ordinarily—they might try to hide it, but a lot of scientists have poetic souls," Davis says. "Art, like science, has to describe the whole word and you can't describe something you're basically clueless about. The most exciting part of these activities is satiating overwhelming curiosity about everything around you." The number of bioartists is still small, Davis says, partly because of a lack of federal funding of the arts in general. Accessibility to the types of equipment bioartists want to experiment with can also be an issue. While Davis has partnered with labs over the past few decades, other artists affiliate themselves with community access laboratories that are run by do-it-yourself biologists. One way that universities can help is to create departmental-wide positions for bioartists to collaborate with scientists. "In the past, there have been artists affiliated with departments in a very utilitarian way to produce figures or illustrations," Church says. "Having someone like Joe stimulates our lab to come together in new ways and if we had more bioartists, I think thinking out of the box would be a more common thing." "In the era of genetic engineering, bioart will gain new meanings and annotations in social and scientific contexts," says Yetisen. "Bioartists will surely take up new roles in science laboratories, but this will be subject to ethical criticism and controversy as a matter of course." More information: Trends in Biotechnology, Yetisen et al.: "Bioart" dx.doi.org/10.1016/j.tibtech.2015.09.
Home > Press > Nanoparticles combine photodynamic and molecular therapies against pancreatic cancer: Novel drug-delivery system cuts off common treatment escape pathways in animal models Abstract: A nanoparticle drug-delivery system that combines two complementary types of anticancer treatment could improve outcomes for patients with pancreatic cancer and other highly treatment-resistant tumors while decreasing toxicity. In their report that has received advance online publication in Nature Nanotechnology, a research team based at the Wellman Center for Photomedicine at Massachusetts General Hospital (MGH) describes how a nanomedicine that combines photodynamic therapy - the use of light to trigger a chemical reaction - with a molecular therapy drug targeted against common treatment resistance pathways reduced a thousand-fold the dosage of the molecular therapy drug required to suppress tumor progression and metastatic outgrowth in an animal model. "A broad challenge in cancer treatment is that tumor cells use a network of cellular signaling pathways to resist and evade treatment," says Bryan Spring, PhD, of the Wellman Center, co-lead author of the report. "The new optically active nanoparticle we have developed is able both to achieve tumor photodamage and to suppress multiple escape pathways, opening new possibilities for synchronized multidrug combination therapies and tumor-focused drug release." Photodynamic therapy (PDT), involves the use of chemicals called photosensitizers that are activated by exposure to specific wavelengths of light to release reactive molecules that can damage nearby cells. In cancer treatment, PDT damages both tumor cells and their blood supply, directly killing some tumor cells and starving those that remain of nutrients. But as with many other types of treatments, treating tumors with PDT can stimulate molecular signaling pathways that support tumor survival. The nanomedicine developed by the Wellman-based team is made up of nanoliposomes - spherical lipid membrane structures - enclosing a polymer nanoparticle that has been loaded with a targeted molecular therapy drug. The lipid membrane of these photoactivable multi-inhibitor nanoliposomes (PMILs) contains a FDA-approved photosensitizer called BPD (benzoporphyrin derivative), and the nanoparticles are loaded with a molecular therapy drug called XL184 or cabozantinib. XL184 inhibits two important treatment escape pathways, VEGF and MET, but while it has FDA approval to treat thyroid cancer and is being tested against pancreatic cancer and several other tumors, it is quite toxic requiring dose restrictions or treatment interruption. Since XL184 is delivered to every part of the body and not just to the tumor when administered orally, enclosing it in the PMIL could reduce toxicity by confining its action to the area of the tumor. Led by Tayyaba Hasan, PhD, of the Wellman Center, the investigators first confirmed in laboratory experiments that exposing PMILs to near-infrared light both activated the antitumor action of BPD and, by disrupting the lipid membrane envelope, released the XL184-containing nanoparticles. In two mouse models of pancreatic cancer, a single treatment consisting of intravenous delivery of the PMILs followed by localized delivery of near-infrared light to the tumor site via optical fibers resulted in significantly greater reduction in tumor size than did either treatment with XL184 or PDT with BPD alone. PMIL treatment also was significantly more effective than treatment with both XL184 and BPD-PDT given as separate agents. Along with prolonged tumor reduction, PMIL treatment also almost completely suppressed metastasis in the mouse models. While the VEGF treatment escape pathway is known to be induced and sensitized by PDT, the research team found that PDT also induces signaling via the MET pathway. The ability to deliver XL184 and PDT almost simultaneously allowed the two therapeutics to be "at the right place at the right time" to cut off the rapid initiation of escape signaling that usually follows PDT. This was reflected in how much more efficient PMIL-delivered treatment was in the animal models compared to either treatment alone, since PDT simultaneously sensitized the tumor to the second therapy. Delivery of XL184 directly to the tumor site produced these promising results at a dosage level less than one thousandth of what is used in oral therapy, with little or no toxicity. "Right now we can say this approach has tremendous potential for patients with locally advanced pancreatic cancer, for whom surgery is not possible," says Hasan. "In our Phase I/II clinical studies with PDT alone, tumor destruction was achieved in all cases, and we've seen at least one case where PDT alone induced enough tumor shrinkage to enable follow-up surgery. The more robust tumor reduction and suppression of escape pathways possible with PMILs might enable curative surgery or improve the outcome of chemotherapy to enhance patient survival. But while we are encouraged by these results, this combination in a new nanoconstruct needs more validation before becoming a clinical treatment option" ### Previously a research fellow in Dermatology at the Wellman Center, Spring is now an assistant professor of Physics at Northeastern University. Hasan is a professor of Dermatology and of Health Sciences and Technology at Harvard Medical School. Bryan Sears and Lei Zak Zheng of the Wellman Center are also first co-authors of the Nature Nanotechnology paper. Additional co-authors are Zhiming Mai, PhD, and Margaret Sherwood, Wellman Center; Reika Watanab and Elizabeth Villa, PhD, University of California San Diego; David Schoenfeld, PhD, MGH Biostatistics; Brian Pogue, PhD, Dartmouth College; and Stephen Pereira, PhD, University College London. This study was supported by National Institutes of Health grants RC1-CA146337, R01-CA160998, P01-CA084203, and F32-CA144210. About Massachusetts General Hospital Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $800 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine. In July 2015, MGH returned into the number one spot on the 2015-16 U.S. News & World Report list of "America's Best Hospitals." For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.