Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Adv Mater. 2019 Oct;31(40):e1902885. doi: 10.1002/adma.201902885. Epub 2019 Aug 18.
Activatable theranostic agents that can be activated by tumor microenvironment possess higher specificity and sensitivity. Here, activatable nanozyme-mediated 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) loaded ABTS@MIL-100/poly(vinylpyrrolidine) (AMP) nanoreactors (NRs) are developed for imaging-guided combined tumor therapy. The as-constructed AMP NRs can be specifically activated by the tumor microenvironment through a nanozyme-mediated "two-step rocket-launching-like" process to turn on its photoacoustic imaging signal and photothermal therapy (PTT) function. In addition, simultaneously producing hydroxyl radicals in response to the high H O level of the tumor microenvironment and disrupting intracellular glutathione (GSH) endows the AMP NRs with the ability of enhanced chemodynamic therapy (ECDT), thereby leading to more efficient therapeutic outcome in combination with tumor-triggered PTT. More importantly, the H O -activated and acid-enhanced properties enable the AMP NRs to be specific to tumors, leaving the normal tissues unharmed. These remarkable features of AMP NRs may open a new avenue to explore nanozyme-involved nanoreactors for intelligent, accurate, and noninvasive cancer theranostics.
可被肿瘤微环境激活的治疗性试剂具有更高的特异性和敏感性。在此，我们开发了一种基于纳米酶介导的 2,2'-联氮双（3-乙基苯并噻唑啉-6-磺酸）（ABTS）负载 ABTS@MIL-100/聚乙烯基吡咯烷酮（AMP）纳米反应器（NRs），用于成像引导的联合肿瘤治疗。所构建的 AMP NRs 可以通过纳米酶介导的“两步火箭发射样”过程被肿瘤微环境特异性激活，从而开启其光声成像信号和光热治疗（PTT）功能。此外，AMP NRs 还可以响应肿瘤微环境中高 H2O2 水平同时产生羟基自由基，并破坏细胞内谷胱甘肽（GSH），从而具有增强的化学动力学治疗（ECDT）能力，与肿瘤触发的 PTT 结合后可获得更有效的治疗效果。更重要的是，H2O2 激活和酸增强特性使 AMP NRs 能够特异性地靶向肿瘤，而对正常组织没有伤害。AMP NRs 的这些显著特性可能为探索基于纳米酶的纳米反应器用于智能、精确和非侵入性癌症治疗开辟了新途径。
