Redox- and MMP-2-sensitive drug delivery nanoparticles based on gelatin and albumin for tumor targeted delivery of paclitaxel

Tumor-responsive nanocarriers are highly valuable and demanded for smart anticancer drug delivery, where a quick release of chemotherapeutic drugs in tumors is preferred. Herein, a redox and MMP-2 sensitive nanoparticle has been designed for targeted delivery of PTX. Bovine serum albumin as a targeting ligand and gelatin as a hydrophilic carrier and MMP-2 sensitive reagent were used to construct the nanoparticles. Disulfide containing prodrug (PTX-SS-COOH) was grafted to the sulfhydryl modified gelatin to form the redox sensitive amphiphilic polymer. The nanoparticles were formed by self-assembly of amphiphilic polymer and BSA covering. Furthermore the modified sulfhydryl group on the gelatin can form a disulfide bond by self-crosslinking in the air, which endows the nanoparticle with a stable structure. The nanoparticle was sensitive to changes in MMP-2 concentration and redox potential, resulting in multiple responsive drug delivery to the tumor microenvironment. We further verified the anticancer effect of the nanoparticles both in vitro and in vivo , the nanoparticle (BSA/Gel-SS-PTX/PTX-SS-COOH NPs) demonstrated an excellent anticancer efficiency.