Synthesis of Copolymers Polyethyleneimine-co-Polyphenylalanine as Gene and Drug Codelivery Carrier

Abstract

In this study, a series of hyperbranched copolymers polyethyleneimine-co-polyphenylalanine (PEI-co-PPhe) are synthesized by ring-opening polymerization with phenylalanine-N-carboxyanhydride as monomer and PEI-25k as initiator, using as a gene and drug codelivery carrier. Among them, PEI-co-PPhe (1:170) is selected out from transfection efficiency and cytotoxicity tests. Then, doxorubicin-cis-aconitic anhydride (CAD) and BCl2-shRNA (as a therapeutic gene) are coloaded into the PEI-co-PPhe carrier to form PEI-co-PPhe/Bcl2-shRNA/CAD complexes as a codeliver system. When the mass ratio of PEI-co-PPhe:Bcl2-shRNA:CAD is 5:1:1, the codeliver system has the most obvious synergistic therapeutic effect against B16F10 cells. Confirmed by confocal laser scanning microscope and flow cytometry, compared with drug and gene alone, the codeliver complexes can be endocytosed into B16F10 cells efficiently. As a result, the appropriate length of PPhe grafted on PEI will improve the gene transfer efficiency and decrease cytotoxicity, as well as effective codelivery of gene and drug into cancer cells to be a promising codelivery carrier for cancer therapy.

Keywords: Bcl2-shRNA; cancer therapy; codelivery; doxorubicin; gene transfection; polyethyleneimine; polyphenylalanine.