Hydrangea-structured tumor microenvironment responsive degradable nanoplatform for hypoxic tumor multimodal imaging and therapy
Hydrangea-structured tumor microenvironment responsive degradable nanoplatform for hypoxic tumor multimodal imaging and therapy
复制标题
绣球花结构肿瘤微环境响应可降解纳米平台用于缺氧肿瘤多模态成像和治疗
DOI：
10.1016/j.biomaterials.2019.03.005
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发表时间：
2019-06-01
期刊：
影响因子：
14
通讯作者：
Dong, Xiaochen
中科院分区：
文献类型：
--
作者：
Tang, Qianyun;Cheng, Zijin;Dong, Xiaochen
研究新的策略来缓解肿瘤缺氧，提高对实体瘤的治疗效果，对肿瘤治疗具有重要意义。本文中，为了克服肿瘤缺氧，将专门设计的aza-BODIPY光敏剂与抗癌药物（阿霉素，DOX）共负载到绣球结构的MnO 2纳米颗粒上，并建立肿瘤微环境（TME）响应性可降解纳米平台（MDSP NP）。MDSP NP（类似于54 nm）具有近红外吸收（类似于853 nm），可以响应于TME而快速解离以产生氧气，从而改善肿瘤缺氧，有利于有效的药物释放和增强的化学/光动力学治疗。通过体内荧光和光声成像显示，MDSP NPs优先积聚在肿瘤部位。光热成像证实，MDSP纳米粒可诱导热疗缓解缺氧，促进治疗性纳米粒的摄取，进一步降低耐药性，提高治疗效率。因此，通过体外和体内研究证实了具有绣球结构的TME响应性氧自生成纳米平台的显着协同肿瘤化学/光动力/光热治疗，证明了其在临床应用中用于缺氧肿瘤治疗的巨大潜力。
Developing new strategies to alleviate tumor hypoxia and enhance the therapeutic efficacy towards solid tumors is of great significance to tumor therapy. Herein, to overcome tumor hypoxia, specifically designed aza-BODIPY photosensitizer is co-loaded with anti-cancer drug (doxorubicin, DOX) onto the hydrangea-structured MnO2 nanoparticles, and a tumor microenvironment (TME) responsive degradable nanoplatform (MDSP NP) is established. MDSP NPs (similar to 54 nm), with near infrared absorption (similar to 853 nm), can be rapidly dissociated to generate oxygen in response to TME, whereby improving tumor hypoxia, in favor of effective drugs release and enhanced chemo/photodynamic therapy. Revealed by in vivo fluorescence and photoaccoustic imaging, MDSP NPs are preferential accumulated at tumor site. Confirmed by photothermal imaging, MDSP NPs can induce hyperthermia to relieve hypoxia, promote the uptake of therapeutic nanoparticles, and further reduce the resistance and improve the therapeutic efficiency. As a result, a remarkable synergistic tumor chemo/photodynamic/photothermal therapy with hydrangea-structured TME responsive oxygen-self-generation nanoplatform is confirmed by both in vitro and in vivo studies, testifying its great potential for hypoxic tumor treatment in clinical application.