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Nano-particles to Target Acidic Tumor Microenvironment for Enhanced Drug Delivery

A team of chemical engineers at MIT has developed a nanoparticle to deliver drugs. The nanoparticle is more acidic than healthy tissues.

According to Paula Hammond, a member of the David H. Koch Institute for Integrative Cancer Research at MIT and chief author of the research paper that has appeared in the journal, ACS Nano, the nano-particle could target all cancer types and carry all drug types.

MIT3’s polymer coating is shed as the particle approaches a tumor, exposing positive charges. Thoscharges help the particle be absorbed through the tumor cell membrane.

The particles are coated with a polymer layer to safeguard them from corrosion by the bloodstream. The team, which included lead author and postdoctoral student Zhiyong Poon, developed the outer layer to drop off after penetrating the acidic environment close to the tumor. This process shows another layer that can enter single cancer cells.

The paper, which appeared online on April 23, says the particles can remain in the bloodstream of mice for a day, assemble close to tumors and penetrate tumor cells. The team exploited tumor acidity caused by its accelerated metabolism. Tumor cells multiply and divide faster than normal cells, and this utilizes more oxygen, enhancing acidity. The tissue becomes increasingly acidic as the tumor grows.

The team used a layer-by-layer assembly technique to develop the technique, in which individual layers could be customized for specific functions. When the external layer fabricated from polyethylene glycol, or PEG disintegrates in the acidic environment, a middle layer that has been positively charged appears. When the particles reach a tumor, they do not penetrate the cells easily. Positively charged particles can enter negatively charged cell membranes, but cannot be injected into the body without coating in order to protect healthy tissues. The inner layer could deliver a cancer drug, or quantum dot for imaging.

Professor of oncology and pharmacology at the University of Texas Southwestern Medical Center, Jinming Gao says this research could help target acidic tumor microenvironment for enhanced drug delivery.

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