固态电子介导的Z-样异质结半导体纳米材料诱导双重程序性细胞死亡用于黑色素瘤治疗

Solid-state electron-mediated z-scheme heterostructured semiconductor nanomaterials induce dual programmed cell death for melanoma therapy

JOURNAL OF NANOBIOTECHNOLOGY

影响因子:12.6

分区:生物学1区 Top / 生物工程与应用微生物1区纳米科技2区

发表日期:2024 Aug 31

作者: Yiping Ren, Yun Wang, Cheng Chen, Xiang Yan, Minghao Chao, Yuting Li, Dehong Yu, Yuqi Huang, Xiaoyang Hou, Fenglei Gao, Guan Jiang, Ming Guan

DOI: 10.1186/s12951-024-02770-4

摘要

程序性细胞死亡（PCD）途径通过清除功能性不足、易感染或潜在致瘤细胞，在维护体内环境的稳定性以及预防癌症和其他疾病中发挥着重要作用。PCD包括多种形式，如凋亡、铜死亡、铁死亡和细胞焦亡。然而，作为诱导PCD的新方法，具有高电子空穴（e-h+）分离能力的新兴固态电子介导的Z-样异质结半导体纳米材料尚未得到充分研究。我们合成了Bi2S3-Bi2O3-Au-PEG纳米棒（BB-A-P NRs）Z-样异质结半导体，具有更高的氧化还原能力和生物相容性。首先，BB-A-P NRs被近红外（NIR）光激发，模拟过氧化氢酶的作用，提供氧气（O2）并通过e-h+转移将其转化为单线态氧（1O2）。其次，它们与肿瘤中的过氧化氢（H2O2）和水（H2O）反应，产生羟基自由基（•OH），诱导细胞凋亡。有趣的是，依赖Caspase-1/Gasdermin D（GSDMD）途径的传统焦亡被激活，伴随由凋亡和活性氧（ROS）引发的细胞焦亡，导致大量损伤相关分子模式（DAMPs）的释放，引起肿瘤细胞的炎症性死亡。反过来，这激活免疫环境，从而实现免疫源性细胞死亡（ICD）。BB-A-P实现了CT成像，便于观察治疗效果。BB-A-P激活的双重PCD被视为一种协调细胞内环境的有效细胞死亡模式，各途径相互关联、相互促进，显示出有前景的治疗效果，并为消除缺氧肿瘤提供了新的策略。

Abstract

The programmed cell death (PCD) pathway removes functionally insignificant, infection-prone, or potentially tumorigenic cells, underscoring its important role in maintaining the stability of the internal environment and warding off cancer and a host of other diseases. PCD includes various forms, such as apoptosis, copper death, iron death, and cellular pyroptosis. However, emerging solid-state electron-mediated Z-scheme heterostructured semiconductor nanomaterials with high electron-hole (e-h+) separation as a new method for inducing PCD have not been well studied. We synthesize the Bi2S3-Bi2O3-Au-PEG nanorods (BB-A-P NRs) Z-scheme heterostructured semiconductor has a higher redox capacity and biocompatibility. Firstly, the BB-A-P NRs are excited by near-infrared (NIR) light, which mimics the action of catalase by supplying oxygen (O2) and converting it to a single-linear state of oxygen (1O2) via e-h+ transfer. Secondly, they react with hydrogen peroxide (H2O2) and water (H2O) in tumor to produce hydroxyl radicals (•OH), inducing apoptosis. Intriguingly, the Caspase-1/Gasdermin D (GSDMD)-dependent conventional pyroptosis pathway induced cellular pyroptosis activated by apoptosis and reactive oxygen species (ROS) which causes the intense release of damage associated molecular patterns (DAMPs), leading to the inflammatory death of tumor cells. This, in turn, activates the immunological environment to achieve immunogenic cell death (ICD). BB-A-P enables computed tomography imaging, which allows for visualization of the treatment. BB-A-P activated dual PCD can be viewed as an effective mode of cell death that coordinates the intracellular environment, and the various pathways are interrelated and mutually reinforcing which shows promising therapeutic effects and provides a new strategy for eliminating anoxic tumors.