Conjugation of paclitaxel on adeno-associated virus (AAV) nanoparticles for co-delivery of genes and drugs.

Abstract We have investigated the use of adeno-associated virus (AAV) nanoparticles as platforms for the co-delivery of genes and drugs to cancer cells. With its regular geometry, nanoscale dimensions, lack of pathogenicity, and high infection efficiency in a wide range of human cells and tissues, AAV is a promising vector for such applications. We tested the covalent conjugation of paclitaxel onto surface-exposed lysine residues present on the virus capsid. Immunoblotting results suggest successful attachment of drug molecules to the virus nanoparticles. Favorably, the reaction conditions did not reduce the gene delivery efficiency of the AAV vectors. Unfortunately, decrease in cancer cell viability was not observed with our AAV–taxol conjugates. For future attempts at conjugating drugs to the AAV nanoparticle, we have identified several improvements than can be considered to achieve the desired cytotoxicity in target cells.