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载药纳米“子弹”经肝动脉栓塞实现肝癌化疗的磁靶向治疗

Janus "nano-bullets" for magnetic targeting liver cancer chemotherapy.

机构信息

Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun 130021, China; CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China; Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.

Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.

出版信息

Biomaterials. 2016 Sep;100:118-33. doi: 10.1016/j.biomaterials.2016.05.030. Epub 2016 May 24.

Abstract

Tumor-targeted delivery of anti-cancer drugs with controlled drug release function has been recognized as a promising strategy for pursuit of increased chemotherapeutic efficacy and reduced adverse effects. Development of magnetic nanoparticulates as delivery carriers to accommodate cytotoxic drugs for liver cancer treatment has evoked immense interest with respect to their convenience in biomedical application. Herein, we engineered multifunctional Janus nanocomposites, characterized by a head of magnetic Fe3O4 and a body of mesoporous SiO2 containing doxorubicin (DOX) as "nano-bullets" (M-MSNs-DOX). This nanodrug formulation possessed nanosize with controlled aspect-ratio, defined abundance in pore structures, and superior magnetic properties. M-MSN-DOX was determined to induce selective growth inhibition to the cancer cell under magnetic field rather than human normal cells due to its preferable endocytosis by the tumor cells and pH-promoted DOX release in the interior of cancer cells. Ultimately, both subcutaneous and orthotropic liver tumor models in mice have demonstrated that the proposed Janus nano-bullets imposed remarkable suppression of the tumor growth and significantly reduced systematic toxicity. Taken together, this study demonstrates an intriguing targeting strategy for liver cancer treatment based on a novel Janus nano-bullet, aiming for utilization of nanotechnology to obtain safe and efficient treatment of liver cancer.

摘要

载药的磁性纳米颗粒作为治疗肝癌的药物载体,因其在生物医学应用方面的便利性而备受关注。本研究设计了一种具有独特结构的多功能Janus 纳米复合材料,其头部为磁性 Fe3O4,主体为载有多柔比星(DOX)的介孔 SiO2(M-MSNs-DOX)。该纳米药物制剂具有纳米尺寸、可控的纵横比、丰富的孔结构和优异的磁性能。由于肿瘤细胞对其具有更好的内吞作用以及在肿瘤细胞内部 pH 促进 DOX 释放,M-MSN-DOX 在磁场下对癌细胞的选择性生长抑制作用强于对人正常细胞的抑制作用。最终,在小鼠的皮下和原位肝癌模型中,所提出的 Janus 纳米子弹显著抑制了肿瘤生长,并显著降低了系统毒性。综上所述,本研究基于新型 Janus 纳米子弹,为肝癌的治疗提供了一种有吸引力的靶向策略,旨在利用纳米技术实现肝癌的安全有效治疗。

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