Biodegradable Metal-Organic Framework-Gated Organosilica for Tumor Microenvironment-Unlocked Glutathione Depletion-Enhanced Synergistic Therapy.
Biodegradable Metal-Organic Framework-Gated Organosilica for Tumor Microenvironment-Unlocked Glutathione Depletion-Enhanced Synergistic Therapy.
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用于肿瘤微环境的可生物降解金属有机框架门控有机二氧化硅解锁谷胱甘肽消耗增强协同疗法。
DOI：
10.1002/adma.202107560
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发表时间：
2021
影响因子：
29.4
通讯作者：
Ju Shenghong
中科院分区：
文献类型：
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作者：
Ma Yuanyuan;Su Zheng;Zhou Liming;He Liangcan;Hou Zhenyu;Zou Jianhua;Cai Yu;Chang Di;Xie Jinbing;Zhu Chen;Fan Wenpei;Chen Xiaoyuan;Ju Shenghong
顺铂（顺二氨二氯铂（II）（CDDP））的临床应用由于非特异性递送和由此产生的严重全身毒性而受到很大限制。小尺寸的生物相容性和可生物降解的中空介孔有机硅（HMOS）纳米颗粒显示出用于靶向CDDP递送的上级优势，但遭受过早的CDDP泄漏。本文中，巧妙地使用了Zn 2 +/Cu 2+共掺杂的金属有机骨架（MOF）来堵塞HMOS的孔，以防止CDDP的潜在泄漏并显著提高HMOS的负载能力。一旦到达酸性肿瘤微环境（TME），外部MOF可以快速分解以释放CDDP用于抗癌化疗。此外，Cu ~（2+）的释放可使细胞内谷胱甘肽（GSH）耗竭，增加CDDP的毒性，并催化肿瘤内H_2O_2分解为高毒性的·OH，用于化学动力学治疗（CDT）。此外，GSH的大幅减少还可以保护产生的·OH不被清除，从而大大提高基于·OH的CDT效果。除了提供混合HMOS@MOF纳米载体外，该研究还有望建立一种新形式的TME解锁纳米制剂，用于高效的肿瘤特异性GSH耗尽增强的协同化疗/化学动力学治疗。
The clinical employment of cisplatin (cis‐diamminedichloroplatinum(II) (CDDP)) is largely constrained due to the non‐specific delivery and resultant serious systemic toxicity. Small‐sized biocompatible and biodegradable hollow mesoporous organosilica (HMOS) nanoparticles show superior advantages for targeted CDDP delivery but suffer from premature CDDP leakage. Herein, the smart use of a bimetallic Zn2+/Cu2+co‐doped metal–organic framework (MOF) is made to block the pores of HMOS for preventing potential leakage of CDDP and remarkably increasing the loading capacity of HMOS. Once reaching the acidic tumor microenvironment (TME), the outer MOF can decompose quickly to release CDDP for chemotherapy against cancer. Besides, the concomitant release of dopant Cu2+can deplete the intracellular glutathione (GSH) for increased toxicity of CDDP as well as catalyzing the decomposition of intratumoral H2O2into highly toxic •OH for chemodynamic therapy (CDT). Moreover, the substantially reduced GSH can also protect the yielded •OH from scavenging and thus greatly improve the •OH‐based CDT effect. In addition to providing a hybrid HMOS@MOF nanocarrier, this study is also expected to establish a new form of TME‐unlocked nanoformula for highly efficient tumor‐specific GSH‐depletion‐enhanced synergistic chemotherapy/chemodynamic therapy.