Hybrid Prodrug Nanoparticles with Tumor Penetration and Programmed Drug Activation for Enhanced Chemoresistant Cancer Therapy

ACS Applied Materials & Interfaces
Caiyan ZhaoYan Wu

Abstract

Despite nanomedicine having shown great potential for reversing cancer cell resistance, the suboptimal transport across multiple biological obstacles seriously impedes its reaching targets at an efficacious level, which remains a challenging hurdle for clinical success in resistant cancer therapy. Here, a lipid-based hybrid nanoparticle was designed to efficiently deliver the therapeutics to resistant cells and treat resistant cancer in vivo. The hybrid nanoparticles (D-NPs/tetrandrine (TET)) are composed of a pH-responsive prodrug 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-doxorubicin (DOX), an efflux inhibitor TET, and a surfactant DSPE-[methoxy (poly(ethylene glycol))-2000] (DSPE-mPEG2000), which hierarchically combatted the sequential physiological and pathological barriers of drug resistance and exhibited prolonged blood circulation, high tumor accumulation, and deep tumor parenchyma penetration. In the meantime, the programmed stepwise activation of encapsulated TET and DOX suppressed the function of resistance-related P-glycoprotein in a timely manner and facilitated the DOX sustained accommodation in tumor cells. Through systematic studies, the results show that such a nanosystem dramatically enhances drug p...Continue Reading

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Citations

May 16, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Shangui LiuGuangxi Zhai

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