Ph-Responsive Drug Delivery System Based on Polymeric Prodrug for Efficient Antitumor Therapy

Abstract

Ph-responsive micellar nanoparticles in nuclear endosomes were prepared by self-assembling amphiphilic poly (ethylene glycol)-Schiff-doxorubicin (PEG-Schiff-DOX, PSD) predrugs. Self-assembly of an amphiphilic poly (ethylene glycol)-Schiff-doxorubicin (PEG-Schiff-DOX, PSD) prodrug was adopted to prepare endosomal pH-responsive micellar nanoparticles, and the encapsulation of free DOX could be made in the hydrophobic core of the nanoparticles by Schiff base bond. These nanoparticles showed great storage steadiness for above 1 week under normal circumstances but disassembled rapidly to answer faintly acidic environment. Thus, we are able to obtain a simple nano-polymer prodrug material that enables efficient and accurate delivery of tumor drugs and can maintain stability in neutral environments and rapidly degrade in the acidic context of tumor cells. In addition, it benefits from the good stability of PSD with high drug loading concentration and long drug release behavior. According to CCK-8 assays, the nanoparticle showed great antitumor activity over free DOX against HeLa tumor cells. These prodrug-based nanomedicines show excellent potential for the development of translational DOX formulations for cancer therapy.