A controlled release system for simultaneous promotion of gene transfection and antitumor effects

Abstract

Chemotherapy combining gene therapy may offer new opportunities in the cancer treatments, so co-delivery of drugs and genes become more and more popular. Among these reports, greatest advantage is the comprehensive effects of genes and drugs. However, it is rarely reports that gene transfection and antitumor effect are promoted simultaneously. In this work, the hyperbranched glycoconjugated polymer is modified with the chlorambucil (CHB) and its chemical structures are well analyzed by Fourier transform infrared spectroscopy (FTIR), ¹H nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The biophysical properties are assessed by transmission electron microscope (TEM) and agarose gel electrophoresis (AGE). Confocal laser scanning microscope (CLSM) and flow cytometry have verified the cell internalization between the carriers and cells. In vitro drug release shows that the drug can slowly release from carrier. Antitumor effect of covalent drug is better than the CHB because the polycations can efficient transport drug into the nucleus. Owning to the hydrophobic modification and CHB controlled released from polycations, grafted polymers show high transfection efficiency than hyperbranched glycoconjugated polymers. All profiles demonstrate that a controlled release carrier of drug can promote gene transfection and antitumor effect, giving a new expectation for the best comprehensive treatment of cancer patients.