A smart tumor-microenvironment responsive nanoprobe for highly selective and efficient combination therapy
A smart tumor-microenvironment responsive nanoprobe for highly selective and efficient combination therapy
复制标题
一种智能肿瘤微环境响应纳米探针，用于高选择性和高效的联合治疗
DOI：
10.1039/c9qi01076a
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发表时间：
2019-12-01
影响因子：
7
通讯作者：
Tang, Yu
中科院分区：
文献类型：
--
作者：
Fan, Yifan;GuaN, Shanli;Tang, Yu
肿瘤缺氧和细胞摄取能力低严重限制了化疗和光动力疗法(PDT)的疗效。因此，我们研制了一种灵巧的肿瘤微环境(TME)响应型纳米探针，它不仅可以增强细胞的摄取能力，提高药物包装效率，调节肿瘤缺氧，而且可以作为Forster共振能量转移(FRET)的受体，实现激发光敏剂的能量猝灭。由于CeOx/Fe_2O_3载体具有海胆状的中空结构，化疗药物阿霉素(DOX)和光敏剂氯e6(Ce6)可以共负载形成CeOx/Fe_2O_3-C&D纳米探针。在正常组织中，CeOx/Fe_2O_3-C&D具有较弱的细胞毒性。在TME中，CeOx/Fe_2O_3纳米壳层开始破裂，DOX在肿瘤部位迅速释放，CeOx/Fe_2O_3表现出类似过氧化氢酶的活性，分解内源性H_2O_2并持续产生O-2以克服原位缺氧。同时，Ce6从“沉默状态”转变为“激活状态”，通过削弱FRET效率产生荧光信号和单线态氧(O-1(2))。因此，我们的研究展示了一种创新的策略，以增强细胞摄取能力，调整肿瘤缺氧，并实现高选择性和特异性的联合治疗。
The therapeutic effects of chemotherapy and photodynamic therapy (PDT) are limited seriously by tumor hypoxia and low cell uptake capacity. Herein, a smart tumor-microenvironment (TME) responsive nanoprobe was developed using pH-responsive and decomposed CeOx/Fe2O3 as a carrier not only to strengthen cell uptake capacity, increase drug packaging efficiency and modulate tumor hypoxia, but also to act as an acceptor of Forster resonance energy transfer (FRET) and achieve energy quenching of an excited photosensitizer. Due to the urchin-like hollow structures of the CeOx/Fe2O3 carrier, the chemotherapy drug doxorubicin (DOX) and the photosensitizer chlorine e6 (Ce6) could be co-loaded to form the nanoprobe CeOx/Fe2O3-C&D. In normal tissue, the nanoprobe CeOx/Fe2O3-C&D showed weak cytotoxicity. Once in the TME, the CeOx/Fe2O3 nanoshells began to break up, DOX was released rapidly at the tumor site, and CeOx/Fe2O3 showed catalase-like activity to decompose endogenous H2O2 and produce O-2 persistently to overcome hypoxia in situ. Meanwhile the Ce6 was transformed from a "silent state" to an "activated state", generating the fluorescence signal and singlet oxygen (O-1(2)) by weakening the FRET efficiency. Therefore, our study showcases an innovative strategy to enhance cell uptake capacity, adjust tumor hypoxia and achieve highly selective and specific combination therapy.