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A boronate-linked linear-hyperbranched polymeric nanovehicle for pH-dependent tumor-targeted drug delivery

机译：一种硼酸盐连接的线性超支化聚合物纳米座，用于pH依赖性肿瘤靶向药物递送

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摘要

Advanced drug delivery systems, which possess post-functionalization feasibility to achieve targetability and traceability, favorable pharmacokinetics with dynamic but controllable stability, and preferable tumor accumulation with prolonged drug residence in disease sites, represent ideal nanomedicine paradigm for tumor therapy. To address this challenge, here we reported a dynamic module-assembly strategy based on reversible boronic acid/1,3-diol bioorthogonality. As a prototype, metastable hybrid nanoself-assembly between hydrophobic hyperbranched diol-enriched polycarbonate (HP-OH) and hydrophilic linear PEG terminated with phenylboronic acid (mPEG-PBA) is demonstrated in vitro and in vivo. The nanoconstruction maintained excellent stability with little leakage of loaded drugs under the simulated physiological conditions. Such a stable nanostructure enabled the effective in vivo tumor accumulation in tumor site as revealed by NIR imaging technique. More importantly, this nanoconstruction presented a pH-labile destruction profile in response to acidic microenvironment and simultaneously the fast liberation of loaded drugs. Accordingly at the cellular level, the intracellular structural dissociation was also proved in terms of the strong acidity in late endosome/lysosome, thus favoring the prolonged retention of remaining drug-loaded HP-OH aggregates within tumor cells. Hence, our delicate design open up a dynamical module-assembly path to develop site and time dual-controlled nanotherapeutics for tumor chemotherapy, allowing enhanced tumor selectivity through prolonged retention of delivery system in tumor cells followed by a timely drug release pattern.
机译：先进的药物递送系统，具有稳定性但可控稳定性，良好的药代动力学，良好的药代动力学，患有疾病部位延长的药物住宿的稳定性，有利的药代动力学，以及患有疾病部位的延长的肿瘤积累。为了解决这一挑战，我们在这里报道了一种基于可逆硼酸/ 1,3-二醇生物正常的动态模块组件策略。作为原型，在体外和体内终止疏水过度富含二醇的聚碳酸酯（HP-OH）和亲水性线性PEG之间的稳定性杂交纳米纤维组件和亲水性线性PEG。在模拟生理条件下，纳米控制保持优异的稳定性，载有载有量的药物泄漏。这种稳定的纳米结构使得在肿瘤部位的体内肿瘤积累中有效，如NIR成像技术所揭示的。更重要的是，该纳米能力呈对酸性微环境的pH-不稳定的破坏曲线，同时释放出载药的快速释放。因此，在细胞水平下，还在晚期内体/溶酶体中的强酸度方面证明了细胞内结构解离，从而有利于在肿瘤细胞内延长保留剩余的药物负载的HP-OH聚集体。因此，我们的精致设计开辟了一种动态模块组装路径，为肿瘤化疗发育现场和时间双控纳米治疗，通过长期保留肿瘤细胞的递送系统随后进行了增强的肿瘤选择性，然后进行了及时的药物释放模式。

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  • 来源
    《Biomaterials》 |2014年第19期|共10页
  • 作者

    JiaH.-Z.; ZhuJ.-Y.; WangX.-L.; ChengH.; ChenG.; ZhaoY.-F.; ZengX.; FengJ.; ZhangX.-Z.; ZhuoR.-X.;

  • 作者单位

    Key Laboratory of Biomedical Polymers of Ministry of Education Department of Chemistry Wuhan;

    State Key Laboratory Breeding Base of Basic Science of Stomatology Department of Oral and;

    Department of Pharmaceutics and Pharmaceutical Chemistry University of Utah Salt Lake City UT;

    Key Laboratory of Biomedical Polymers of Ministry of Education Department of Chemistry Wuhan;

    State Key Laboratory Breeding Base of Basic Science of Stomatology Department of Oral and;

    State Key Laboratory Breeding Base of Basic Science of Stomatology Department of Oral and;

    Key Laboratory of Biomedical Polymers of Ministry of Education Department of Chemistry Wuhan;

    Key Laboratory of Biomedical Polymers of Ministry of Education Department of Chemistry Wuhan;

    Key Laboratory of Biomedical Polymers of Ministry of Education Department of Chemistry Wuhan;

    Key Laboratory of Biomedical Polymers of Ministry of Education Department of Chemistry Wuhan;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物医学工程;
  • 关键词

    Boronate linkage; Dual-controlled drug delivery; Nanoassembly; Passive tumor targeting; PH-sensitivity;

    机译：硼酸盐;双控药物递送;纳米组织;被动肿瘤靶向;pH敏感性;

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