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首页> 外文期刊>Advanced Functional Materials >Treatment of Malignant Brain Tumor by Tumor-Triggered Programmed Wormlike Micelles with Precise Targeting and Deep Penetration
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Treatment of Malignant Brain Tumor by Tumor-Triggered Programmed Wormlike Micelles with Precise Targeting and Deep Penetration

机译：肿瘤靶向程序化蠕虫状胶束精确靶向和深层穿透治疗恶性脑肿瘤

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摘要

The efficient and specific drug delivery to brain tumor is a crucial challenge for successful systemic chemotherapy. To overcome these limitations, here a tumor-triggered programmed wormlike micelle is reported with precise targeting and deep penetration to treat malignant gliomas, which is composed of pH-responsive mPEG-b-PDPA copolymer and bioreducible cyclic RGD peptide targeted cytotoxic emtansine (DM1) conjugates (RGD-DM1). The RGD-DM1 loaded nanoscaled wormlike micelles (RNW) exhibit nanometer-sized wormlike assemblies with the transverse diameter of 21.3 +/- 1.8 nm and length within 60-600 nm, and the RGD targeting peptide in RNW is 4.2% in weight. RNW can be dissociated at intracellular acidic environments to release RGD-DM1, and be further degraded into DM1 by cleavage of disulfide bonds in the reductive milieu. In particular, by exploiting the unique wormlike structure and the RGD targeting peptide modification, RNW can be endowed with obviously enhanced drug delivery to brain, precise targeting to brain tumor, deep penetration into tumor mass, and efficient internalization into glioma cells in a programmed manner, thereby surprisingly leading to an 88.9% inhibition on tumor progression in an orthotopic brain tumor model. Therefore, the properly designed RNW can provide a promising delivery platform for systemic chemotherapy of brain tumor.
机译：有效和特异性地将药物递送至脑肿瘤是成功进行全身化疗的关键挑战。为了克服这些限制，这里报道了一种由肿瘤触发的程序化蠕虫状胶束，具有精确的靶向性和深层穿透性，可治疗恶性神经胶质瘤，该胶质瘤由pH响应性mPEG-b-PDPA共聚物和可生物还原的环RGD肽靶向的细胞毒性翡翠（DM1）组成共轭物（RGD-DM1）。负载RGD-DM1的纳米级蠕虫胶束（RNW）表现出纳米级蠕虫状装配体，其横向直径为21.3 +/- 1.8 nm，长度在60-600 nm之内，并且RNW中的RGD靶向肽的重量为4.2％。 RNW可以在细胞内酸性环境中解离以释放RGD-DM1，并通过还原性环境中二硫键的裂解进一步降解为DM1。特别是，通过利用独特的蠕虫状结构和RGD靶向肽修饰，RNW可以显着增强向大脑的药物输送，对脑肿瘤的精确靶向，对肿瘤块的深入渗透以及以编程方式有效内化到神经胶质瘤细胞中，从而令人惊讶地导致原位脑肿瘤模型对肿瘤进展的抑制率为88.9％。因此，合理设计的RNW可以为脑肿瘤的全身化疗提供有希望的传递平台。

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  • 来源
    《Advanced Functional Materials》 |2016年第23期|4201-4212|共12页
  • 作者

    Zeng Lijuan; Zou Lili; Yu Haijun; He Xinyu; Cao Haiqiang; Zhang Zhiwen; Yin Qi; Zhang Pengcheng; Gu Wangwen; Chen Lingli; Li Yaping;

  • 作者单位

    Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China|Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China|Shenyang Pharmaceut Univ, Sch Pharm, Shenyang 110016, Peoples R China;

    Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China|Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China|Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China;

    Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China|Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China;

    Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China|Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China;

    Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China|Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China;

    Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China|Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China;

    Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China|Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China;

    Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China|Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China;

    Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China|Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China;

    Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China|Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China;

    Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China|Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China;

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