Focus
Dr. Omid Farokhzad’s Laboratory of Nanomedicine and Biomaterials focuses on the development of nanoparticle delivery systems that are capable of delivering large numbers of cytotoxic or therapeutic molecules to targeted cancer cells. More recently his group has developed multifunctional nanoscale systems for combined imaging, sensing, and therapeutic applications. “The thrust of our interest,” he emphasizes, “is on the therapeutic side.”
Background
Dr. Farokhzad grew up in Connecticut and attended the University of Massachusetts and Boston University School of Medicine. He completed a residency in anesthesiology at Brigham and Women’s Hospital and a two-year postdoctoral fellowship in Professor Robert Langer’s laboratory at the Massachusetts Institute of Technology (MIT). Dr. Farokhzad explains that his “background in molecular and cell biology was a nice match with Dr. Langer’s multidisciplinary laboratory where the focus was on material science and technology, and in particular, nanotechnology, tissue engineering, and drug delivery.” It was during his post-doctoral training at MIT that Dr. Farokhzad began to develop theories about ways to apply nanoscale drug delivery systems to new cancer therapies. As Dr. Farokhzad says, “I had the luxury of training in a very special environment, one that permitted me to do virtually any science I wished provided it had the potential for clinical utility. I was interested in doing translational research that might actually move quickly from the bench to bedside, improving lives.” In 2004, Dr. Farokhzad returned to Brigham and Women’s Hospital as a staff anesthesiologist, later bringing the fruits of his efforts at MIT in the form of his portion of a 20 million dollar grant from the National Cancer Institute to the MIT-Harvard Center for Cancer Nanotechnology Excellence. He is currently an assistant professor in the Department of Anesthesia.
Research
Early work done in close collaboration with the laboratory of Professor Robert Langer at MIT focused on targeted delivery of drugs to cancer cells. “That work” Dr. Farokhzad explains, “gave us an appreciation for the challenges and opportunities that exist for using nanoparticle delivery systems, which can deliver thousands of molecules of drug with each biorecognition or binding event.” Dr. Farokhzad initially used prostate cancer as a model to demonstrate proof of concept of these targeted nanoparticles. The results of this work were widely praised by academic, government, and industry news agencies, for example, ABC news, Popular Science cover article, Scientific American, Technology Review, NCI Bulletin, BWH press, and NSTI. More recently, his group developed targeted nanoparticles for the treatment of breast cancer and postangioplasty restenosis, and they are actively collaborating with other laboratories to develop nanoparticles for pancreatic and ovarian cancers. Dr. Farokhzad’s research could have far-reaching implications for treating cancers and other diseases beyond the current approaches. Rather than attempting to “engineer” the single best nanoparticle system, Dr. Farokhzad says that “an alternative approach would be to develop a library of many different and unique nanoparticles, each with its own complement of distinct characteristics (e.g., size, ligands, charge, surface hydrophilicity), and then do functional screens with library components to determine which disease-specific nanoparticle delivery system works best for that particular tumor or disease.” This approach, which is a central part of the project that Dr. Farokzad heads within the Center for Cancer Nanotechnology Excellence, is progessing very nicely, “well beyond our highest expectations.” The truly unique aspect of Dr. Farokhzad’s system, however, is the addition of multi-functionality. Thus, the nanodelivery systems developed in his laboratory include indicator elements that signal when the drug is delivered to the tumor cell. This provides information about the location of the tumor, as well as the efficacy of the drug, which in turn provides information about the stage of the patient's tumor as well as its response to treatment. The applications of Dr. Farokzhad's cutting edge technology are not limited to cancer, and nanoparticle drug delivery systems are also being developed in his lab for cardiovascular disease.
Laboratory
Dr. Farokhzad’s laboratory presently has a staff of six, including four postdoctoral fellows and 1 student.
Funding
Research in the Laboratory of Nanomedicine and Biomaterials is supported by the MIT-Harvard Center for Cancer Nanotechnology Excellence from the National Cancer Institute, National Institute of Biomedical Imaging and Bioengineering, and by a
multi-institutional grant from the Prostate Cancer Foundation.
Collaborations
The laboratory has extensive active collaborations inside the Brigham; at adjacent institutions most notably, MIT, DFCI, and Harvard Medical School; nationally and internationally, including groups in Cornell Medical School, South Korea and Italy who are working with Dr. Farokhzad’s group to develop nanoparticles for cancer therapy.
Importance of Being at the Brigham
When asked to comment on the importance of multidisciplinary collaboration to scientific discovery, Dr. Farokhzad points to his laboratory’s experience with prostate cancer. “We sat down with the oncologists and urologists to determine the best drug for treating prostate cancer.” We relied on their expertise to answer the question, “How much drug should we deliver to the prostate and what are the unique characteristics of prostate cancer that we should be aware of when we engineer nanoparticles?” He adds, “We spoke with senior pharmaceutical experts who had worked with polymer particle development for other drug delivery systems and asked a very important question: Is the FDA likely to approve our system for clinical use, and if not, why? We brought these collaborators to the table and listened to their advice. When they disagreed with our approach, we went back to the drawing board and redesigned our system.”
Future
Dr. Farokhzad looks forward to testing these disease-specific delivery vehicles for cancer therapy in more sophisticated studies using larger animal models with a view towards clinical application in humans. “Our central goal is to develop technologies that have the potential to reach the clinic,” but the rate-limiting step is additional funding to advance the work, from proof-of-concept research in small animals, to large animal toxicology studies under the Good Laboratory Practice (GLP) guides, as required by the Food and Drug Administration (FDA) before support will be given for a clinical trial. From a scientific perspective, Dr. Farokhzad points to a general obstacle, which has hindered the clinical translation of various nanoparticle platforms, namely, the body’s own defense system, whose job it is to clear the drugcontaining particles. This problem requires engineering of particles that can evade the immune system while finding target cells for delivering the intended therapeutic effect. “Our approach” Dr. Farokhzad explains, “has been to develop nanoparticles from components that have already been approved by the FDA for other clinical indications, therefore making it more likely that the system will be better tolerated in the human body. Dr. Farokhzad is reluctant to make future predictions and espouses a more practical approach to targeted polymeric nanoparticle development that relies on solid technological advances. However, when asked about the long-range view, Dr. Farokhzad surmises, “I think that the real impact of nanotechnology in the long-run for oncology will come with systemically administered nanoparticles that not only image and treat, but also can sense and detect very early cancerous changes at a time when they can be readily treated.”
Selected References
Farokhzad OC, Jon S, Khademhosseini A, Tran T-N, LaVan DA. Langer R. Nanoparticle-Aptamer Bioconjugates: A New Approach for Targeting Prostate Cancer Cells. Cancer Res. 2004;64:7668-7762.
Farokhzad OC, Cheng J, Teply BA, Sherifi I, Jon S, Kantoff PW, Richie JP, Langer R. Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proc Natl Acad Sci. 2006;103:6315-6320.
Bagalkot V, Zhang L, Levy-Nissembaum E, Jon S, Kantoff PW, Langer R, Farokhzad OC. Quantum Dot-Aptamer Conjugates for Synchronous Cancer Imaging, Therapy, and Sensing of Drug Delivery Based on Bi-Fluorescence Resonance Energy Transfer. Nano Letters 2007, 7:3065-3070
Zhang L, Radovic-Moreno AF, Alexis F, Gu FX, Basto PA, Bagalkot V, Jon S, Langer R, Farokhzad OC. Aptamer-doxorubicin physical conjugate as a novel targeted drug delivery platform. ChemMedChem 2007, 2:1268-71
Cheng J, Teply BA, Sherifi I, Jon SY, Sung J, Luther G, Gu FX, Levy-Nissenbaum E, Langer R and Farokhzad OC. Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery. Biomaterials 2007, 28:869-876
Gu FX, Zhang L, Teply BA, Mann N, Wang A, Radovic-Moreno AF, Langer R, Farokhzad OC. Precise engineering of targeted nanoparticles using self-assembled biointergrated block copolymers. Proc Natl Acad Sci (in-press)
This page was last modified on 7/7/2007
