Near infrared light triggered reactive oxygen species responsive nanoparticles for chemo-photodynamic combined therapy
Near infrared light triggered reactive oxygen species responsive nanoparticles for chemo-photodynamic combined therapy
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近红外光触发活性氧响应纳米粒子用于化学光动力联合治疗
DOI：
10.1039/c8tb00308d
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发表时间：
2018
影响因子：
7
通讯作者：
Zhao Chunshun
中科院分区：
文献类型：
--
作者：
Zhang Xuefei;Huang Binyao;Shen Yifeng;Yang Chanzhen;Huang Zeqian;Huang Yanjuan;Xu Xiaoyu;Jiang Yali;Sun Xiaoqi;Li Xining;Yan Mina;Zhao Chunshun
目前，将光动力疗法（PDT）与化疗相结合以提高癌症治疗效率的策略引起了广泛的关注。然而，局部浓度低、药物释放不可控、治疗光源不合适、对PDT肿瘤部位的反应低等缺点导致联合治疗效果不理想。为此，我们提出了一种简单智能的、具有ros反应的酞菁锌敏化二氧化钛纳米粒子，该纳米粒子与氯苯（CBL） （mTiO2 - BCBL@ZnPC NPs）偶联，试图解决这些问题。纳米颗粒不仅在近红外辐射（NIR）下触发PDT，产生多种活性氧（ROS），而且通过CBL与纳米颗粒之间的苯硼酯的裂解，实现了主要活性氧H2O2对CBL的可控释放。令人印象深刻的是，CBL在近红外照射下的可控释放表现出开关特性和时间依赖性。此外，mTiO2 - BCBL@ZnPC纳米粒子的平均直径为30 nm，具有良好的稳定性和生物相容性。体外细胞毒性研究表明，mTiO2 - BCBL@ZnPC NPs在近红外照射下比mTiO2@ZnPC NPs和CBL具有更强的细胞毒性，而在黑暗条件下，mTiO2 - BCBL@ZnPC NPs的细胞毒性较小。上述结果表明，光控药物释放具有选择性高、安全性好、副作用小等优点，是一种很有前景的癌症治疗方法，有望用于化学-光动力联合治疗，提高治疗效率。
Currently, the strategy of combining photodynamic therapy (PDT) and chemotherapy for enhancing cancer therapeutic efficiency has aroused extensive interest. Nonetheless, weaknesses such as low local concentration, uncontrollable release of the drug, a non-suitable treatment light source, and a low response to the tumor site of PDT lead to the combined treatment effect not being ideal. Herein, we proposed simple and intelligent ROS-responsive zinc phthalocyanine sensitized TiO2 nanoparticles which conjugated with chlorambucil (CBL) (mTiO2–BCBL@ZnPC NPs) in an attempt to solve these issues. Not only were the nanoparticles triggered in near infrared radiation (NIR) for PDT with various reactive oxygen species (ROS) being generated, but the nanoparticles also realized the controllable release of CBL by H2O2, a major kind of ROS, through cleavage of the phenylboronic ester between CBL and the nanoparticle. Impressively, the controllable release of CBL under NIR irradiation showed an on–off characteristic and time dependency. In addition, the well-defined mTiO2–BCBL@ZnPC NPs with a 30 nm average diameter showed good stability and biocompatibility. The in vitro cytotoxicity studies demonstrated that the mTiO2–BCBL@ZnPC NPs were more cytotoxic under NIR irradiation than the mTiO2@ZnPC NPs and CBL, while the mTiO2–BCBL@ZnPC NPs were less cytotoxic under dark conditions. The above results implied that photo-controlled drug release is a promising choice for cancer therapy due to its high selectivity, good safety and low side-effects, and would be expected to be used in chemo-photodynamic combined therapy for improving the therapeutic efficiency.