Nanotechnology Meets Cancer

The subject at the CIMIT Forum on Jan. 29 was “Nanotechnology Meets Cancer,” and the well-attended event was held at the Beth Israel Deaconess Medical Center.

One speaker was Shiladitya Sengupta, assistant professor of medicine and health sciences and technology, Harvard Medical School, Brigham & Women’s Hospital and MIT.

Also presenting was Raghu Kalluri, PhD, professor of medicine, Harvard Medical School, Department of Biological Chemistry and Pharmacology, Harvard-MIT Division of Health Sciences and Technology; chief, Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center.

Moderating Dr. Sengupta’s session was Jose Miguel Trevejo, MD, PhD, senior scientist, Biomedical Engineering Group, the Charles Stuart Draper Laboratory, Department of Infectious Disease, BIDMC.

Moderating the Kalluri session was Jeffrey Borenstein, PhD, director, Biomedical Engineering Center, program leader for biomaterials and tissue engineering, and Draper Laboratory Site Miner for CIMIT.

Nanotechnologies are increasingly useful in the management of cancer. Nanoscale devices can impact cancer biology at three levels: early detection using nanocantilevers or nanoparticles (for example); tumor imaging using radiocontrast nanoparticles or quantum dots; and drug delivery using nanovectors and hybrid nanoparticles. Dr. Sengupta focused on the major milestones in the integration of nanotechnology and cancer biology, and the future of nanoscale approaches for cancer management.

Dr. Sengupta discussed current developments in his laboratory in the hybrid nanotechnologies.  He noted that his team has created a company called Tempo Pharmaceutical. Since 2005 it has raised about $22 million.  Based on technology licensed from MIT, Tempo is focused on improving the efficacy and safety profile of existing and new drugs employing advances in nanotechnology.

The company utilizes its proprietary nanocell technology to develop multi-compartmental, nanoparticle-based therapeutics in which two drugs with varied release rates are packaged within a single nanoparticle. This approach allows for sequential delivery of drugs, optimizing the location, rate of release and synergistic effect of the two therapies while minimizing toxicities.

Dr. Kalluri’s lab is evaluating the role of non-cancer cells in cancer progression and metastasis. He discussed the roles of extra-cellular matrix, angiogenesis, fibroblast recruitment and innate maturity in cancer progress and metastasis. He also discussed the “host defense,” and how host responses are recruited to control cancer progression or further aid in tumor growth.

     

Nanodevices for Cancer Therapy

The idea of building structures atom by atom has been around for decades, but only recently have researchers gained the tools to make nanotechnology a reality.  In medicine, there are many opportunities for nanotechnology to improve the care that patients receive.  Nanodevices are already being developed for use as biosensors, as part of imaging systems, and as drug delivery vehicles.  All three of these functions promise to help improve cancer therapy.

Angiogenesis, or the formation of new blood vessels, plays a major role in the development of a tumor.  After a tumor has grown to about the size of a cubic millimeter, its core becomes hypoxic, and it begins to release growth factors to recruit new blood vessels that will supply it with oxygen.  Inhibiting angiogenesis has been investigated as a means of preventing tumor growth but has not proven to be fully successful, for tumor cells cut off from the blood supply can eventually develop “reactive resistance” to hypoxia.  These resistant cancer cells could be killed by chemotherapeutic drugs, but once the vasculature to the tumor has been cut off, there is no way for chemotherapy to be delivered.  Nanotechnology offers a way to deliver chemotherapeutic drugs and anti-angiogenic drugs in the same vehicle so that as the blood supply is shut off, chemotherapy is present to prevent any hypoxia-resistant cells from proliferating.

The lab of Shiladitya Sengupta is in the process of developing nanocells capable of delivering both types of drugs.  Each nanocell is between 120 and 200 μm in diameter and can be thought of as “a balloon within a balloon.”  Inside each nanocell is a chemotherapeutic drug covalently bound to a polymer, and on the surface of each cell is a lipid coat containing an anti-angiogenic drug.  The technology makes use of the fact that a tumor’s blood vessels have pores 600 μm in diameter and are much leakier than normal blood vessels, which have pores only around 50 μm in diameter.  The nanocells circulate in the blood, and because of their size, they leak out of blood vessels only in tumors.  Once there, the nanocells are degraded by enzymes produced by the tumor.  Work remains to be done to win clinical approval for the technology, but results from Sengupta’s lab indicate that the nanocells are more effective and less toxic than traditional chemotherapy.     

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