Enhanced drug targeting by attachment of an anti alphav integrin antibody to doxorubicin loaded human serum albumin nanoparticles.

Abstract

Specific transport of anti-cancer drugs into tumor cells may result in increased therapeutic efficacy and decreased adverse events. Expression of alphavbeta3 integrin is enhanced in various types of cancer and monoclonal antibodies (mAbs) directed against alphavbeta3 integrins hold promise for anti-cancer therapy. DI17E6 is a monoclonal antibody directed against alphav integrins that inhibits growth of melanomas in vitro and in vivo and inhibits angiogenesis due to interference with alphavbeta3 integrins. Here, DI17E6 was covalently coupled to human serum albumin nanoparticles. Resulting nanoparticles specifically targeted alphavbeta3 integrin positive melanoma cells. Moreover, doxorubicin loaded DI17E6 nanoparticles showed increased cytotoxic activity in alphavbeta3-positive melanoma cells than the free drug. Therefore, DI17E6-coupled human serum albumin nanoparticles represent a potential delivery system for targeted drug transport into alphavbeta3-positive cells.