Stimuli-Responsive Polymeric Nanoparticles for On-Demand Drug Release in Cancer Therapy

Abstract

The use of stimuli-responsive polymeric nanoparticles has become a superior system towards controlled and site-specific drug delivery in cancer therapy. Biocompatible polymeric nanoparticles were designed in this study such that they can be used in on-demand release of drugs based on tumor-related stimuli to improve therapeutic efficiency and reduce systemic toxicity. Polyethylene glycol (PEG)-functionalized poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles were prepared by the solvent evaporation method and doxorubicin, a model anticancer drug, was loaded into them. Functionalities such as stimulus-responsive pH- and redox-sensitive linkages were added to take advantage of the acidic and reducing tumor microenvironment. The prepared nanoparticles had a narrow size distribution, stable negative surface charge that was attributed to uniform nanoscale size and colloidal stability that facilitated accumulation in the tumor through the enhanced permeability and retention (EPR) effect. The encapsulation efficiency (>75) and drug loading was high, with the optimized formulation showing encapsulation efficiency of more than 90. In vitro drug release experiments indicated a low rate of drug release under physiological conditions (pH 7.4) whereas faster rate of drug release under tumor-mimicking conditions (pH 5.5) indicated successful stimuli-triggered behavior. Cellular uptake experiments indicated that internalization of the nanoparticles was significantly increased over that of the free drug leading to increased availability of the drug in the intracellular environment. Moreover, cytotoxicity experiments showed that drug loaded nanoparticle showed much greater anticancer effect compared to free doxorubicin, and blank nanoparticle showed no significant toxicity, which validated carrier biocompatibility. Generally, the findings underscore the promise of stimuli-responsive polymeric nanoparticles as one of the promising approaches in precision-guided, on-demand delivery of drugs in the treatment of cancer, which overcomes major challenges of traditional chemotherapy.