Folate-targeting and reduction-responsive nano-delivery system based on curcumin polymer to enhance the anti-cancer activity

In this article, folic acid (FA) modified biodegradable poly (ethylene glycol) (PEG 2K ) was chosen as the polymeric skeleton to conjugate with curcumin (CUR) via a disulfide bond to construct a reduction-responsive drug delivery system (FA-PEG 2K -SS-CUR), aiming at improving the solubility of CUR and providing a targeted, efficient, and low side-effect anti-cancer nano-preparation. The polymers were synthesized through three steps to develop FA-PEG 2K -SS-CUR micelles, with a drug loading capacity of up to 10.9% and good stability. The particle of FA-PEG 2K -SS-CUR micelles determined by Malvern Mastersizer was 79.14±2.2 nm, and a hemolysis assay confirmed their good biocompatibility. The reduction sensitivity of FA-PEG 2K -SS-CUR micelles was verified by adding dithiothreitol (DTT) to the release medium, showing a programmed drug release mode with 60.41% released within 72 h, indicating a certain sustained-release capability. In vitro cytotoxicity assays showed that the FA-PEG 2K -SS-CUR micelles were more cytotoxic than free CUR. Additionally, FA-PEG 2K -SS-CUR micelles exhibited a higher cellular uptake rate than micelles without FA. Hence, the prepared multifunctional FA-PEG 2K -SS-CUR micelles is a promising anti-tumor nano-preparation.