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Endogenous reactive oxygen species burst induced and spatiotemporally controlled multiple drug release by traceable nanoparticles for enhancing antitumor efficacy

机译：内源性活性氧物种突发诱导和不可避免的纳米颗粒通过可追踪的多种药物释放，用于增强抗肿瘤功效

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摘要

Reactive oxygen species (ROS) are not only used as a therapeutic reagent in chemodynamic therapy (CDT), to stimulate the release of antineoplastic drugs, they can also be used to achieve a combined effect of CDT and chemotherapy to enhance anticancer effects. Herein, we synthesized a pH-responsive prodrug (PEG(2k)-NH-N-DOX), ROS-responsive prodrug (PEG(2k)-S-S-CPT-ROS), organic CDT agents (TPP-PEG(2k)-LND, TPP-PEG(2k)-TOS), and T1-enhanced magnetic resonance imaging contrast agents (Gd-DTPA-N16-16), and used them to encapsulate combrestatinA4 (CA4) to prepare traceable pH/ROS dual-responsive multifunctional nanoparticles (TLDCAG NPs) with endogenous ROS burst and spatiotemporally controlled multiple drug release ability. Firstly, TLDCAG NPs were accumulated in the tumor cell microenvironment via an enhanced permeability and retention (EPR) effect. Secondly, CA4 was released and specifically destroyed angiogenesis to facilitate the interaction between the tumor and the remaining TLDCG NPs. After accumulating in tumor cells, the TLDCG NPs could be destroyed under acidic conditions to quickly release doxorubicin (DOX), TPP-PEG(2k)-LND, and TPP-PEG(2k)-TOS. Thirdly, TPP-PEG(2k)-LND and TPP-PEG(2k)-TOS quickly targeted mitochondria, induced endogenous ROS bursts, reduced the mitochondrial membrane potential, and induced tumor cell apoptosis. Endogenous ROS can not only be used as a therapeutic reagent for CDT, but also can cut off the thioketal bond in PEG(2k)-S-S-CPT-ROS and release camptothecin (CPT). Finally, TLDCAG NPs were traced by magnetic resonance imaging (MRI). Furthermore, in vitro and vivo results indicate that the TLDCAG NPs have vigorous antitumor activity and negligible systemic toxicity. Therefore, the TLDCAG NPs provide an efficient strategy for enhancing antitumor efficacy.
机译：活性氧（ROS）不仅用作化学动力学治疗（CDT）的治疗试剂，刺激抗肿瘤药物的释放，它们也可用于达到CDT和化疗的综合作用，以提高抗癌效果。在此，我们合成了pH-响应性前药（PEG（2K）-NH-N-DOX），ROS响应性前药（PEG（2K）-SS-CPT-ROS），有机CDT试剂（TPP-PEG（2K） - LND，TPP-PEG（2K）-TOS）和T1增强磁共振成像造影剂（GD-DTPA-N16-16），并用它们封装了Combreastin4（CA4）以制备可追踪的pH / ROS双响应多功能纳米粒子（TLDCAG NPS）具有内源性ROS突发和时尚控制的多种药物释放能力。首先，通过增强的渗透率和保留（EPR）效应，TLDCAG NPS在肿瘤细胞微环境中积累。其次，释放CA4并特别破坏血管生成，以促进肿瘤与剩余TLDCG NP之间的相互作用。在肿瘤细胞积累后，TLDCG NP可以在酸性条件下破坏，以快速释放多柔比蛋白（DOX），TPP-PEG（2K）-LND和TPP-PEG（2K）-TOS。第三，TPP-PEG（2K）-LND和TPP-PEG（2K）-TOS快速靶向线粒体，诱导内源性ROS爆发，降低线粒体膜电位，并诱导肿瘤细胞凋亡。内源性ROS不仅可以用作CDT的治疗试剂，而且可以切断PEG（2K）-S-S-CPT-ROS中的硫酮键并释放捕获喜树碱（CPT）。最后，磁共振成像（MRI）追踪TLDCAG NP。此外，体外和体内结果表明TLDCAG NPS具有剧烈的抗肿瘤活性和可忽略的全身毒性。因此，TLDCAG NPS提供了提高抗肿瘤效力的有效策略。

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  • 来源
    《Biomaterials Science》 |2021年第14期|共16页
  • 作者

    Wang Ning; Liu Chenyu; Yao Weihe; Zhou Hengjun; Yu Simiao; Chen Hailiang; Qiao Weihong;

  • 作者单位

    Dalian Univ Technol Sch Chem Engn State Key Lab Fine Chem Dalian 116024 Peoples R China;

    Dalian Univ Technol Sch Chem Engn State Key Lab Fine Chem Dalian 116024 Peoples R China;

    Dalian Univ Technol Sch Chem Engn State Key Lab Fine Chem Dalian 116024 Peoples R China;

    Dalian Univ Technol Sch Chem Engn State Key Lab Fine Chem Dalian 116024 Peoples R China;

    Dalian Univ Technol Sch Chem Engn State Key Lab Fine Chem Dalian 116024 Peoples R China;

    Dalian Univ Technol Sch Chem Engn State Key Lab Fine Chem Dalian 116024 Peoples R China;

    Dalian Univ Technol Sch Chem Engn State Key Lab Fine Chem Dalian 116024 Peoples R China;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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