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Highly-controllable drug release from core cross-linked singlet oxygen-responsive nanoparticles for cancer therapy

机译：来自核心交联单次氧响应纳米粒子的可高度可控药物释放用于癌症治疗

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Highly-controllable release consisting of preventing unnecessary drug leakage at physiologically normal tissues and triggering sufficient drug release at tumor sites is the main aim of nanoparticle-based tumor therapy. Developing drug-conjugation strategies with covalent bonds in response to a characteristic stimulus, such as reactive oxygen species (ROS) generated by photodynamic therapy (PDT) has attracted much attention. ROS can not only cause cytotoxicity, but also trigger the cleavage of ROS-responsive linkers. Therefore, it is feasible to design a new model of controlled drug release via the breakage of ROS-responsive linkers and degradation of nanoparticles. The self-supply of the stimulus and highly-controllable drug release can be achieved by encapsulation of photosensitizer (PS) and chemotherapeutic drugs simultaneously without any support of tumor endogenous stimuli. Therefore, we used thioketal (TK) linkers as the responsive linkers due to their reaction with singlet oxygen (O-1(2), SO), a type of ROS. They were conjugated to the side groups of polyphosphoesters (PPE) via click chemistry to acquire the core cross-linked SO-responsive PPE nanoparticles poly(thioketal phosphoesters) (TK-PPE). TK-PPE coated with the photosensitizer chlorin e6 (Ce6) and chemotherapeutic drug doxorubicin (DOX) simultaneously were prepared and named as TK-PPECe6&DOX. TK-PPECe6&DOX kept stable due to the high stability of the TK-linkers in the normal physiological environment. With self-production of SO as the stimulating factor from the encapsulated Ce6, highly-controlled drug release was achieved. After incubation of tumor cells, 660 nm laser irradiation induced SO generation, resulting in the cleavage of TK-linkers and boosted-release of DOX. Highly-controllable drug release of TK-PPECe6&DOX through self-production of stimulus increased antitumor efficacy, offering a promising avenue for clinical on-demand chemotherapy.
机译：高度可控的释放，包括防止在生理正常组织中的不必要的药物泄漏，并在肿瘤部位引发足够的药物释放是基于纳米粒子的肿瘤疗法的主要目的。响应于通过光动力治疗（PDT）产生的特征刺激（例如反应性氧物质（ROS）的特征刺激而产生具有共价键的药物 - 缀合策略（PDT）引起了很多关注。 ROS不仅会引起细胞毒性，还可以触发ROS响应式接头的切割。因此，通过响应ROS响应性接头和纳米颗粒的降解，设计新的受控药物释放模型是可行的。通过同时封装光敏剂（PS）和化学治疗药物，可以通过肿瘤内源性刺激的任何载体封装光敏剂（PS）和化学治疗药物来实现刺激和高度可控药物释放的自供应。因此，由于它们与单线氧（O-1（2），SO），一种ROS的反应，我们使用硫代汗（TK）接头作为响应性接头。它们通过点击化学与聚磷酸酯（PPE）的侧组缀合，以获取核心交联的所响应PPE纳米颗粒Poly（Thioketal磷酸酯）（TK-PPE）。制备涂有光敏剂氯庚烷E6（CE6）和化学治疗药物多柔比星（DOX）的TK-PPE，并命名为TK-PPECE6＆DOX。 TK-PPECE6＆DOX由于TK-Linkers在正常生理环境中的高稳定性而保持稳定。随着封装的CE6的刺激因子的自我生产，实现了高度控制的药物释放。孵育肿瘤细胞后，诱导660nm激光照射所以生成，导致TK接头的切割和DOX的增强释放。通过刺激的自我生产增加抗肿瘤功效，通过刺激的自我生产，高度可控的药物释放TK-PPECE6和DOX，为临床按需化疗提供了有希望的大道。

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  • 来源
    《RSC Advances》 |2020年第34期|共12页
  • 作者

    Zhou Jiayan; Sun Chunyang; Yu Chunshui;

  • 作者单位

    Tianjin Med Univ Dept Radiol Gen Hosp Tianjin 300052 Peoples R China;

    Tianjin Med Univ Dept Radiol Gen Hosp Tianjin 300052 Peoples R China;

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  • 正文语种 eng
  • 中图分类 化学;
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