Nanocarrier for augmenting the efficacy of reactive oxygen species (ROS) by tumor microenvironment (TME) has become an emerging strategy for cancer treatment. Herein, a smart biodegradable drug delivery nanoplatform with mitochondrial-targeted ability, pH-responsive drug release and enzyme-like catalytic function is designed. This efficient ROS-generating platform uses ultrasound with deeper penetration capability as excitation source for combined chemotherapy and sonodynamic therapy (SDT) of tumor. In vitro experiments show that the nanoplatform can co-load Ce6 and DOX and be degraded in slight acid environment, and the DOX release rate is 63.91 ± 1.67%. In vivo experiments show that the nanoplatform has extremely biosafety and can be enriched in tumor site and excluded from body after 24 h. More significantly, after combined treatment, the tumors are eliminated and the mice still survive healthily without recurrence after 60 d. This is because not only it can achieve mitochondrial targeting and use platinum particle to increase oxygen content in TME to enhance the effect of SDT, but also it can use weak acidic TME to accelerate drug release to achieve the combination of chemotherapy and SDT. The probe provides a new strategy for designing ROS-based nanoplatform for the treatment of malignant tumor.

中文翻译：

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ROS增强和肿瘤微环境响应生物可降解纳米平台，可增强化学-声动力学治疗。

通过肿瘤微环境（TME）增强活性氧（ROS）功效的纳米载体已成为一种新兴的癌症治疗策略。在这里，设计了一种具有线粒体靶向能力，pH响应药物释放和酶样催化功能的智能生物可降解药物输送纳米平台。这个高效的ROS生成平台使用具有更强穿透能力的超声作为激发源，用于肿瘤的联合化学疗法和声动力疗法（SDT）。体外实验表明，该纳米平台可以同时负载Ce6和DOX，并在弱酸性环境中降解，其DOX释放率为63.91±1.67％。体内实验表明，纳米平台具有极高的生物安全性，并且可以在肿瘤部位富集，并且在24小时后可以从体内排除。更重要的是，经过综合治疗，消灭了肿瘤，小鼠在60 d后仍然健康地存活，没有复发。这是因为它不仅可以实现线粒体靶向，并利用铂颗粒增加TME中的氧含量来增强SDT的作用，而且还可以利用弱酸性TME来加速药物释放，从而实现化学疗法和SDT的结合。该探针为设计用于治疗恶性肿瘤的基于ROS的纳米平台提供了新的策略。