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Targeted Self-assembly of Renal Clearable Cu2-xSe to Induce Lysosome Swelling for Multimodal Imaging Guided Photothermal/Chemodynamic Synergistic Therapy
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2022-10-10 , DOI: 10.1002/adfm.202208354 Xiaowei Luan 1 , Yongchun Pan 1 , Yuyu Zhou 2 , Dongtao Zhou 1 , Wenjian Zhao 1 , Fei Zeng 1 , Zhenxing Zhu 1 , Qiangbing Lu 2 , Qianglan Lu 1 , Yanfeng Gao 1 , Guanzhong He 1 , Minghui Lu 2 , Yujun Song 1
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2022-10-10 , DOI: 10.1002/adfm.202208354 Xiaowei Luan 1 , Yongchun Pan 1 , Yuyu Zhou 2 , Dongtao Zhou 1 , Wenjian Zhao 1 , Fei Zeng 1 , Zhenxing Zhu 1 , Qiangbing Lu 2 , Qianglan Lu 1 , Yanfeng Gao 1 , Guanzhong He 1 , Minghui Lu 2 , Yujun Song 1
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Renal clearance is critical for nanodrug to avoid the long-term body retention-related side effects, while it is difficult to achieve efficient tumor accumulation and retention. The over-developed lysosomes in cancer cells have become an emerging target for more precise and effective cancer therapy. Herein, a pH-responsive reversible self-assembled Cu2-xSe-BSA, which can be renal cleared under neutral or basic conditions, is developed for selectively targeted aggregation in cancer lysosomes with enhanced tumor accumulation and retention. Moreover, the aggregation of Cu2-xSe-BSA can enhance the photoacoustic imaging signal, photothermal therapy, and chemodynamic therapy capability. Cu2-xSe-BSA accumulated in lysosomes cannot only induce lysosomes swelling, but also generate reactive oxygen species in situ, causing lysosomal membrane permeabilization and finally lysosomal cell death. Notably, the assembled Cu2-xSe-BSA can dissociate to be renal clearable after the treatments are completed and left the acid tumor microenvironment, being of great significance both in scientific research and clinical trial.
中文翻译：
肾脏可清除 Cu2-xSe 的靶向自组装诱导溶酶体肿胀用于多模式成像引导的光热/化学动力学协同治疗
肾脏清除对于纳米药物避免长期体内滞留相关的副作用至关重要，但难以实现有效的肿瘤积累和滞留。癌细胞中过度发育的溶酶体已成为更精确、更有效的癌症治疗的新兴靶点。在此，开发了一种 pH 响应性可逆自组装 Cu 2- x Se-BSA，它可以在中性或碱性条件下被肾脏清除，用于在癌症溶酶体中选择性靶向聚集，增强肿瘤积累和保留。此外，Cu 2- x Se-BSA 的聚集可以增强光声成像信号、光热疗法和化学动力学疗法能力。铜2- x溶酶体中积累的 Se-BSA 不仅会引起溶酶体肿胀，还会在原位产生活性氧，导致溶酶体膜透化，最终导致溶酶体细胞死亡。值得一提的是，组装后的Cu 2- x Se-BSA在治疗结束后可解离为肾脏可清除，离开酸性肿瘤微环境，在科学研究和临床试验中均具有重要意义。
更新日期：2022-10-10
中文翻译：
肾脏可清除 Cu2-xSe 的靶向自组装诱导溶酶体肿胀用于多模式成像引导的光热/化学动力学协同治疗
肾脏清除对于纳米药物避免长期体内滞留相关的副作用至关重要，但难以实现有效的肿瘤积累和滞留。癌细胞中过度发育的溶酶体已成为更精确、更有效的癌症治疗的新兴靶点。在此，开发了一种 pH 响应性可逆自组装 Cu 2- x Se-BSA，它可以在中性或碱性条件下被肾脏清除，用于在癌症溶酶体中选择性靶向聚集，增强肿瘤积累和保留。此外，Cu 2- x Se-BSA 的聚集可以增强光声成像信号、光热疗法和化学动力学疗法能力。铜2- x溶酶体中积累的 Se-BSA 不仅会引起溶酶体肿胀，还会在原位产生活性氧，导致溶酶体膜透化，最终导致溶酶体细胞死亡。值得一提的是，组装后的Cu 2- x Se-BSA在治疗结束后可解离为肾脏可清除，离开酸性肿瘤微环境，在科学研究和临床试验中均具有重要意义。
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