New Technique Selectively Eradicates Cancer Cells

A graduate student and biomedical engineer's innovations in the area of cancer therapy, specifically two inventions in nanomedicine, has resulted in a new class of cancer therapeutics and a new paradigm for enhancing drug delivery to tumors.

Geoffrey von Maltzahn, a 28-year-old Ph.D. candidate in the Harvard-Massachusetts Institute of Technology-[MIT] Division of Health Sciences and Technology (HST; Cambridge, MA, USA) is currently helping to tackle one of the world's biggest challenges: improving tumor detection and therapeutic delivery to boost the survival rate of cancer patients. He has received the US$30,000 Lemelson-MIT Student Prize for his promising innovations in the area of cancer therapy.

Cancer currently kills more people worldwide than HIV/AIDS, tuberculosis, and malaria combined. In spite of the billions of dollars invested into drug development and decades of research, selectively killing cancer cells has remained an elusive goal. Chemotherapies, a common class of cancer treatments, are intended to kill the fast-growing cells that form tumors. However, these drugs travel throughout the entire body, and often affect normal, healthy tissue along with cancer cells, causing side effects such as hair loss, nausea, anemia, and even nerve and muscle problems. Furthermore, resistance to these drugs can occur and can cause even initially successful treatment regimens to fail.

Working at the confluence of nanotechnology, engineering, and medicine, Mr. von Maltzahn's innovations have the potential to reduce side effects and overpower drug resistance mechanisms by more powerfully concentrating external energy and targeted therapeutics in tumors. Since 2004, Mr. von Maltzahn has worked closely with his advisor, Dr. Sangeeta N. Bhatia, an electrical engineering and computer science professor in the Harvard-MIT Division of HST, to devise innovative treatments that could precisely target and destroy tumor cells without affecting healthy tissue. Seeking to improve the specificity of cancer ablation--the destruction of tumors through the application of heat--Mr. von Maltzahn developed polymer-coated gold "nanoantennas” that can target tumors and convert benign-infrared light into heat.

The nanoparticles were designed to be injected intravenously, where they circulate through the bloodstream and progressively concentrate at the tumor site by infiltrating pores in rapidly growing tumor blood vessels. Once in the tumor, the antennas can be precisely heated with a noninvasive, near-infrared light to specifically kill the cancerous cells. "The polymer coated gold nanoantennas are the longest-circulating and most efficiently heated to date,” stated Dr. Bhatia. "Preclinical trials reveal that a single intravenous nanoparticle injection eradicated 100% of tumors in mice using a near-infrared light. The results of these trials are very promising, meaning that the impact of this technology is wide-reaching with many potential applications.”

Mr. Von Maltzahn's second invention aims to essentially improve the intravenous delivery of therapeutics to tumors by taking a "systems” approach to their design. This work draws on insights from biologic systems, such as ants foraging and bees swarming, where relatively simple methods of communication can lead to very sophisticated system behaviors.

Inspired by the potential for inter-nanoparticle communication to improve therapeutics' ability to find tumors, Mr. von Maltzahn invented a series of ways for nanoparticles to communicate with each another in the body. One technique involves benign "scout" particles initially locating the tumor, and once inside, sending powerful signals to recruit secondary, "assassin" particles that contain the therapeutics. In preclinical trials, this system has been able to deliver over 40-times higher doses of therapeutics to tumors in mice, in comparison to noncommunicating control nanoparticles.

"If such highly-targeted delivery can be achieved clinically, this method would enable doctors to increase the drug dose that is delivered to tumors, increasing its overall efficacy and reducing side-effects,” Mr. von Maltzahn explained. "This concept of engineering systems of nanoparticles that collectively outsmart disease barriers has many potential applications in medicine, from improving regenerative medicines to ultrasensitive diagnostics.”

Mr. Von Maltzahn's research has already made a considerable impact scientifically and commercially, resulting in eight patent applications, 19 submitted or published papers, and his founding roles in two companies: Nanopartz, Inc. and Resonance Therapeutics.

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Harvard-MIT Division of Health Sciences and Technology