Construction of the biocompatible and pH-sensitive prodrug nanoparticles via the self-assembly for improving tumor therapy

Abstract

Endosomal pH-responsive micellar nanoparticles were prepared by self-assembly of a macromolecular poly(ethylene glycol)-Schiff-Doxorubicin (PEG-Schiff-DOX) prodrug.. These nanoparticles exhibited excellent storage stability for over 1 week under normal conditions, but disassembled quickly in response to faintly acidic environment. According to the EPR effect, the surface pore diameter of tumor blood vessels can reach hundreds of nanometers, while the surface pore diameter of ordinary blood vessels does not exceed 20 nanometers. Therefore, the chemical assembly of the drug is designed to have a diameter of 20-200 nanometers, thereby greatly improving the selectivity of the drug for tumor cells. Additionally, benefitting from the difference in drug release mechanism and rate between encapsulated DOX and conjugated DOX, a programmed drug release behavior was observed, which may result in higher intracellular drug concentration and longer action time. CCK-8 assays showed that the nanoparticles demonstrated superior antitumor activity than free PTX against both HeLa cells. These nanomedicines, which utilize prodrugs, exhibit immense promise in the advancement of translational DOX formulations for cancer treatment.