GOLD NANOPARTICLES-BASED NEW FORMULATION USEFUL FOR CANCER THERAPY

摘要

The current invention relates to development of new formulation containing gold nanoparticles (AuNPs) with bi-functional recombinant fusion proteins TRAF(C) for the delivery of anticancer drugs and nucleic acids to HER2+ cancers. Using the combinatorial approach, we designed gold nanoparticle-based targeted drug delivery system (TDDS) or (Au-TR-DX-si) by combining AuNPs with bi-functional recombinant fusion protein TRAF(C) (TR), doxorubicin (DX) and siRNA (si). The recombinant protein based gold nanoparticles formulations are stable and homogenous as revealed by several physicochemical studies. In addition, the engineered fusion protein TRAF(C) has the ability to target selectively to HER2+ receptors (heregulin receptors .also,known as .human,epidermalžgr.owth,factor, receptor-2) overexpressed in o.varianžcancer cells. (SK-OV-3). The functional activity of the nanoformulation was further evaluated both in vitro and in vivo. Intraperitoneal administration of this formulation in SK-OV-3 xenograft nude mice exhibited significant suppression of tumor growth due to co-delivery of ErbB2 siRNA and doxorubicin. In vivo biodistribution confirmed increased accumulation of gold in tumor tissue which further established the targeting property of the nanoconjugation. Based on these studies, we strongly believe that the nanomedicine-based formulation could be developed as a universal strategy for effective treatment of HER2+ cancers.