Ma Zhaoyu, Zhang Jin, Zhang Weiyun, Foda Mohamed F, Zhang Yifan, Ge Lin, Han Heyou
State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, P. R. China.
State Key Laboratory of Agricultural Microbiology, College of Science, Huazhong Agricultural University, Wuhan, Hubei 430070, P. R. China; Department of Biochemistry Faculty of Agriculture, Benha University, Moshtohor, Toukh 13736, Egypt.
iScience. 2020 May 22;23(5):101049. doi: 10.1016/j.isci.2020.101049. Epub 2020 Apr 13.
Currently, patients receiving cancer treatments routinely suffer from distressing toxic effects, most originating from premature drug leakage, poor biocompatibility, and off-targeting. For tackling this challenge, we construct an intracellular Ca cascade for tumor therapy via photothermal activation of TRPV1 channels. The nanoplatform creates an artificial calcium overloading stress in specific tumor cells, which is responsible for efficient cell death. Notably, this efficient treatment is activated by mild acidity and TRPV1 channels simultaneously, which contributes to precise tumor therapy and is not limited to hypoxic tumor. In addition, Ca possesses inherent unique biological effect and normal cells are more tolerant of the undesirable destructive influence than tumor cells. The Ca overload leads to cell death due to mitochondrial dysfunction (upregulation of Caspase-3, cytochrome c, and downregulation of Bcl-2 and ATP), and in vivo, the released photothermal CuS nanoparticles allow an enhanced 3D photoacoustic imaging and provide instant diagnosis.
目前，接受癌症治疗的患者经常遭受令人痛苦的毒副作用，其中大多数源于药物过早泄漏、生物相容性差和脱靶效应。为应对这一挑战，我们通过光热激活TRPV1通道构建了一种用于肿瘤治疗的细胞内钙级联反应。该纳米平台在特定肿瘤细胞中产生人工钙超载应激，这是导致细胞有效死亡的原因。值得注意的是，这种高效治疗由轻度酸性和TRPV1通道同时激活，这有助于精确的肿瘤治疗，并且不限于缺氧肿瘤。此外，钙具有固有的独特生物学效应，正常细胞比肿瘤细胞对不良破坏影响更具耐受性。钙超载由于线粒体功能障碍（半胱天冬酶-3、细胞色素c上调，以及Bcl-2和ATP下调）导致细胞死亡，在体内，释放的光热硫化铜纳米颗粒可增强三维光声成像并提供即时诊断。
