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Multifunctional Shell-Core Nanoparticles for Treatment of Multidrug Resistance Hepatocellular Carcinoma

机译：多功能壳核纳米颗粒治疗多药耐药性肝细胞癌

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摘要

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.
机译：多药耐药（MDR）是肝癌化疗中的主要障碍。本文报道了一种可生物降解的多功能靶向肿瘤的核壳结构纳米载体（RGD肽功能化纳米颗粒，RGD-NPs），用于治疗MDR肝细胞癌，它由三个部分组成：pH触发的磷酸钙外壳，长循环磷脂酰丝氨酸-聚乙二醇（PS-PEG）核心，以及活性靶向配体RGD肽。将抗药性抑制剂（维拉帕米，VER）和化学治疗剂（米托蒽醌，MIT）分别封装在外壳层和内芯层中，以获得负载VER和MIT的RGD-NP（VM-RGD-NP）。由于壳核结构，VER和MIT可以顺序释放，因此协同减弱了MDR细胞对MIT的外排作用。同样，磷酸钙可通过变化的pH值引发溶酶体逸出。结合优化的MDR肿瘤细胞内在化途径，可以提高细胞内有效化疗药物的浓度，从而达到提高疗效的目的。在该系统中，PEG延长了体内循环时间。而且，相对于非靶向纳米颗粒，肽RGD明显增加了对MDR肿瘤的亲和力。结果，VM-RGD-NP对MDR肝细胞癌显示出显着的协同作用，为MDR肿瘤提供了有希望的治疗方法。

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  • 来源
    《Advanced Functional Materials》 |2018年第14期|1706124.1-1706124.17|共17页
  • 作者

    Wang Qi; Zhang Xiangyu; Liao Hongze; Sun Ying; Ding Li; Teng Yanwei; Zhu Wei-Hong; Zhang Zhirong; Duan Yourong;

  • 作者单位

    Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst,State Key Lab Oncogenes & Rela, Shanghai 200032, Peoples R China;

    Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst,State Key Lab Oncogenes & Rela, Shanghai 200032, Peoples R China;

    Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst,State Key Lab Oncogenes & Rela, Shanghai 200032, Peoples R China;

    Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst,State Key Lab Oncogenes & Rela, Shanghai 200032, Peoples R China;

    Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst,State Key Lab Oncogenes & Rela, Shanghai 200032, Peoples R China;

    Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst,State Key Lab Oncogenes & Rela, Shanghai 200032, Peoples R China;

    East China Univ Sci & Technol, Sch Chem & Mol Engn, Key Lab Adv Mat, Shanghai 200237, Peoples R China;

    Sichuan Univ, West China Sch Pharm, Minist Educ, Key Lab Drug Targeting & Novel Drug Delivery Syst, Chengdu 610041, Sichuan, Peoples R China;

    Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst,State Key Lab Oncogenes & Rela, Shanghai 200032, Peoples R China;

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  • 正文语种 eng
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  • 关键词

    core-shell structures; hepatic carcinomas; multidrug resistance; multifunctional nanoparticles; sequential administration;

    机译：核-壳结构;肝癌;多药耐药性;多功能纳米颗粒;顺序给药;

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