Nanoparticle: Monoclonal Antibody Conjugates: A Novel Drug Delivery System in Human Breast Cancer

摘要

The goal of this research project was to develop a novel targeted drug delivery system which would allow delivery of drugs directly to cancerous breast tissue without delivering significant amounts of drug to other parts of the body. The systems described in this research proposal utilize biodegradable nanoparticles based on poly(lactic-co- glycolic) acid (PLAGA) containing paclitaxel (Taxol) or doxorubicin (adriamycin). The nanoparticles were prepared according to a novel technique which incorporates poly(ethylene glycol) (PEG) into the nanoparticles. Addition of PEG alone reduces the uptake of the nanoparticles by the reticuloendothelial system and increases their circulation time. In addition, the PEG arms of the nanoparticles were to be conjugated to monoclonal antibody (MAb) to HER-2/neu, which would selectively bind to breast cancer cells expressing the HER-2 extracellular domain, thereby allowing the nanoparticles to be delivered and targeted directly to cancerous breast tissue. Some nanoparticles are also prepared using polymers that are graft copolymers of PEG and PLA/PGA. All formulations of nanoparticles were to be prepared in order to be of a size less than 750 nm in diameter, preferably less than 300 nm.