Zwitterionic shielded polymeric prodrug with folate-targeting and pH responsiveness for drug delivery.

摘要: Zwitterionic polymers are a class of that acts as both Lewis base and acid in solution. These not only have excellent properties hydration, anti-bacterial adhesion, charge reversal easy chemical modification, but also characteristics long-term circulation suppress nonspecific protein adsorption vivo. Here, we describe novel folate-targeted acid-labile polymeric prodrug under the microenvironment tumor cells, abbreviated FA-P(MPC-co-PEGMA-BZ)-g-DOX, which was synthesized via combination reversible addition–fragmentation chain transfer (RAFT) copolymerization, Schiff-base reaction, Click chemistry, reaction between amine group doxorubicin (DOX) aldehyde functionalities P(MPC-co-PEGMA-BZ) pendants, wherein MPC PEGMA-BZ represent 2-(methacryloyloxy)ethyl phosphorylcholine polyethylene glycol methacrylate ester benzaldehyde, respectively. The could self-assemble into nanoparticles an aqueous average particle size morphologies were observed by dynamic light scattering (DLS) transmission electron microscopy (TEM), We investigated vitro drug release behavior rapid nanoparticle dissociation mildly acidic microenvironment. methyl thiazolyl tetrazolium (MTT) assay verified copolymer possessed good biocompatibility FA-P(MPC-co-PEGMA-BZ)-g-DOX showed higher cellular uptake than those without FA moiety. results cytotoxicity intracellular non-folate/folate targeted further confirmed be efficiently accumulated rapidly internalized HeLa cells due to strong interaction multivalent (PC) groups cell membranes. This kind multifunctional with combined target-ability pH responsiveness demonstrates promising potential for cancer chemotherapy.