Multifunctional Shell–Core Nanoparticles for Treatment of Multidrug Resistance Hepatocellular Carcinoma. (22nd January 2018)

• Record Type: Journal Article
• Authors: Wang, Qi; Zhang, Xiangyu; Liao, Hongze; Sun, Ying; Ding, Li; Teng, Yanwei; Zhu, Wei‐Hong; Zhang, Zhirong; Duan, Yourong
• Is Part Of: Advanced functional materials. Volume 28:Number 14(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-01-22
• Subjects: core–shell structures -- hepatic carcinomas -- multidrug resistance -- multifunctional nanoparticles -- sequential administration; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.201706124
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract: Multidrug resistance (MDR) is the main obstruction against the chemotherapy for hepatocellular carcinoma. Herein, a biodegradable multifunctional tumor‐targeted core–shell structural nanocarrier (RGD peptide functionalized nanoparticles, RGD‐NPs) is reported for treating MDR hepatocellular carcinoma, which consists of three components: pH‐triggered calcium phosphate shell, long circulation phosphatidylserine‐polyethylene glycol (PS‐PEG) core, and an active targeting ligand RGD peptide. Drug‐resistance inhibitor (verapamil, VER) and chemotherapeutic agent (mitoxantrone, MIT) are separately encapsulated into the outer shell layer and inner core layer to obtain VER and MIT loaded RGD‐NPs (VM‐RGD‐NPs). Due to the shell–core structure, the VER and MIT can release sequentially, thus synergistically weakening the efflux effect to MIT by MDR cells. Also, the calcium phosphate can trigger lysosomal escaping through the varied pH value. Together with the optimized internalization pathway in MDR tumor cells, the increased intracellular effective chemotherapeutic drug concentration can be realized, thus achieving the improved curative effect. In this system, the PEG extends the circulation time in vivo. Also, the peptide RGD distinctly increases the affinity to MDR tumors with respect to nontargeted nanoparticles. As a consequence, VM‐RGD‐NPs exhibit a significant synergistic effect toward the MDR hepatocellular carcinoma, providing a promising therapeutic approach for MDR tumor. Abstract : A biodegradable multifunctional tumor‐targeted core–shell structural nanocarrier (RGD‐NPs) for treating multidrug resistance hepatocellular carcinoma, which consists of three components: pH‐triggered calcium phosphate shell, long circulation phosphatidylserine‐polyethylene glycol core, and an active targeting ligand RGD peptide. Drug‐resistance inhibitor (verapamil) and chemotherapeutic agent (mitoxantrone) are separately encapsulated into the outer shell layer and inner core layer.