Multifunctional Nanoparticles as Nanocarrier for Vincristine Sulfate Delivery To Overcome Tumor Multidrug Resistance

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Abstract

Multifunctional nanoparticles, Fol/R7 NPs, based on pH-sensitive PLGA-PEG-folate and cell penetrating peptide R7-conjugated PLGA-PEG, were constructed for targeting vincristine sulfate (VCR) to tumor and overcoming multidrug resistance (MDR). In this study, the pH-triggered VCR release was 65.6% during 8 h in pH 5.0, but only 35.8% in pH 7.4, demonstrating that a large amount of VCR released rapidly at weak acidic environment. The VCR-Fol/R7 NPs could significantly enhance cellular uptake and cytotoxicity in MCF-7 and MCF-7/Adr cells when compared to the nanoparticles solely modified by folate or R7. With folate receptor-mediated endocytosis and strong intracellular penetration, VCR-Fol/R7 NPs increased drug accumulation in resistant tumor cells by escaping P-glycoprotein mediated drug efflux. In vivo imaging suggested the active targeting attributed to pH sensitivity and folate receptor-mediated effect could improve tumor targeting efficacy. Indeed, VCR-Fol/R7 NPs exhibited the stongest antitumor efficacy in vivo. Therefore, Fol/R7 NPs are an effective nanocarrier for delivering antitumor drug and overcoming multidrug resistance.

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