Microchimica Acta ( IF 5.3 ) Pub Date : 2021-04-06 , DOI: 10.1007/s00604-021-04810-4
Hang He 1 , Song Meng 1 , Haimin Li 1 , Qingyuan Yang 1 , Ziqiang Xu 1 , Xueqin Chen 1 , Zhengguang Sun 1 , Bingbing Jiang 1 , Cao Li 1
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Mitochondria, as the energy factory of most cells, are not only responsible for the generation of adenosine triphosphoric acid (ATP) but also essential targets for therapy and diagnosis of various diseases, especially cancer. The safe and potential nanoplatform which can deliver various therapeutic agents to cancer cells and mitochondrial targeted imaging is urgently required. Herein, Au nanoparticles (AuNPs), mesoporous silica nanoparticles (MSN), cationic ligand (triphenylphosphine (TPP)), doxorubicin (DOX), and carbon nanodots (CDs) were utilized to fabricate mitochondrial targeting drug delivery system (denoted as CDs(DOX)@MSN-TPP@AuNPs). Since AuNPs, as the gatekeepers, can be etched by intracellular glutathione (GSH) via ligand exchange induced etching process, DOX can be released into cells in a GSH-dependent manner which results in the superior GSH-modulated tumor inhibition activity. Moreover, after etching by GSH, the CDs(DOX)@MSN-TPP@AuNPs can serve as promising fluorescent probe (λex = 633 nm, λem = 650 nm) for targeted imaging of mitochondria in living cells with near-infrared fluorescence. The induction of apoptosis derived from the membrane depolarization of mitochondria is the primary anti-tumor route of CDs(DOX)@MSN-TPP@AuNPs. As a kind of GSH-responsive mitochondrial targeting nanoplatform, it holds great promising for effective cancer therapy and mitochondrial targeted imaging.
Graphical abstract
中文翻译：
基于 GSH 响应性介孔二氧化硅纳米粒子的纳米平台用于癌症治疗和线粒体靶向成像
线粒体作为大多数细胞的能量工厂，不仅负责三磷酸腺苷（ATP）的产生，而且是治疗和诊断各种疾病，尤其是癌症的重要靶点。迫切需要能够将各种治疗剂输送到癌细胞和线粒体靶向成像的安全和潜在的纳米平台。在此，金纳米粒子（AuNPs）、介孔二氧化硅纳米粒子（MSN）、阳离子配体（三苯基膦（TPP））、多柔比星（DOX）和碳纳米点（CDs）被用来制造线粒体靶向药物递送系统（表示为CDs（DOX） )@MSN-TPP@AuNPs)。由于 AuNPs 作为守门人，可以通过配体交换诱导蚀刻过程被细胞内谷胱甘肽 (GSH) 蚀刻，DOX 可以以 GSH 依赖性方式释放到细胞中，从而产生优异的 GSH 调节的肿瘤抑制活性。此外，经过GSH蚀刻后，CDs(DOX)@MSN-TPP@AuNPs可以作为有前景的荧光探针（λ ex = 633 nm，λ em = 650 nm) 用于使用近红外荧光对活细胞中的线粒体进行靶向成像。线粒体膜去极化诱导细胞凋亡是CDs(DOX)@MSN-TPP@AuNPs的主要抗肿瘤途径。作为一种谷胱甘肽响应性线粒体靶向纳米平台，它在有效的癌症治疗和线粒体靶向成像方面具有广阔的前景。
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