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首页> 外文期刊>Advanced Functional Materials >A Sequentially Triggered Nanosystem for Precise Drug Delivery and Simultaneous Inhibition of Cancer Growth, Migration, and Invasion
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A Sequentially Triggered Nanosystem for Precise Drug Delivery and Simultaneous Inhibition of Cancer Growth, Migration, and Invasion

机译：顺序触发的纳米系统，用于精确的药物递送和癌症生长，迁移和侵袭的同时抑制。

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摘要

The rational design of cancer-targeted and bioresponsive drug delivery vehicles can enhance the anticancer efficacy of conventional chemotherapeutics and reduce their adverse side effects. However, the complexity of precise delivery and the ability to trigger drug release in specific tumor sites remain a challenging puzzle. Here, a sequentially triggered nanosystem composed of HER2 antibody with disulfide linkage as a surface decorator (HER2@NPs) is constructed for precise drug delivery and the simultaneous inhibition of cancer growth, migration, and invasion. The nanosystem actively accumulates in cancer cells, undergoes self-immolative cleavage in response to biological thiols, and is degraded to form small nanoparticles. After internalization by receptor-mediated endocytosis, the nanoparticles further disassemble under acidic conditions in the presence of lysozymes and cell lysates, leading to sequentially triggered drug release. The released payload triggers overproduction of reactive oxygen species and activates p53 and MAPKs pathways to induce cancer cell apoptosis. Moreover, HER2@NPs markedly suppress the migration and invasion of human bladder cancer cells at nontoxic concentrations. HER2@NPs demonstrate potent in vivo anticancer efficacy, but show no obvious histological damage to the major organs. Taken together, this study provides a valid tactic for the rational design of sequentially triggered nanosystems for precise drug delivery and cancer therapy.
机译：合理设计针对癌症且具有生物反应性的药物输送工具，可以增强常规化学疗法的抗癌功效，并减少其不良副作用。然而，精确递送的复杂性和在特定肿瘤部位触发药物释放的能力仍然是一个具有挑战性的难题。此处，构建了由具有二硫键作为表面修饰剂（HER2 @ NPs）的HER2抗体组成的顺序触发纳米系统，用于精确的药物递送并同时抑制癌症的生长，迁移和侵袭。纳米系统活跃地积聚在癌细胞中，响应于生物硫醇而经历自消灭性裂解，并降解形成小的纳米颗粒。通过受体介导的内吞作用内在化后，纳米颗粒在溶菌酶和细胞裂解物存在的酸性条件下进一步分解，导致依次触发药物释放。释放的有效载荷触发了活性氧的过度产生，并激活了p53和MAPKs途径来诱导癌细胞凋亡。此外，HER2 @ NPs在无毒浓度下能显着抑制人膀胱癌细胞的迁移和侵袭。 HER2 @ NPs在体内具有有效的抗癌功效，但对主要器官没有明显的组织学损害。综上所述，这项研究为合理设计顺序触发的纳米系统以提供精确的药物输送和癌症治疗方法提供了有效的策略。

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  • 来源
    《Advanced Functional Materials》 |2016年第43期|7775-7790|共16页
  • 作者

    Liu Ting; Lai Lanhai; Song Zhenhuan; Chen Tianfeng;

  • 作者单位

    Jinan Univ, Dept Chem, Guangzhou 510632, Guangdong, Peoples R China;

    Jinan Univ, Dept Chem, Guangzhou 510632, Guangdong, Peoples R China;

    Jinan Univ, Dept Chem, Guangzhou 510632, Guangdong, Peoples R China;

    Jinan Univ, Dept Chem, Guangzhou 510632, Guangdong, Peoples R China;

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