Zhang Hanjie, Zhang Yitong, Zhang Yushi, Li Hanyue, Ou Meitong, Yu Yongkang, Zhang Fan, Yin Huijuan, Mao Zhuo, Mei Lin
State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, PR China.
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore, Singapore.
Nat Commun. 2024 Aug 8;15(1):6783. doi: 10.1038/s41467-024-50769-0.
Although nanocatalytic medicine has demonstrated its advantages in tumor therapy, the outcomes heavily relie on substrate concentration and the metabolic pathways are still indistinct. We discover that violet phosphorus quantum dots (VPQDs) can catalyze the production of reactive oxygen species (ROS) without requiring external stimuli and the catalytic substrates are confirmed to be oxygen (O) and hydrogen peroxide (HO) through the computational simulation and experiments. Considering the short of O and HO at the tumor site, we utilize calcium peroxide (CaO) to supply catalytic substrates for VPQDs and construct nanoparticles together with them, named VPCaNPs. VPCaNPs can induce oxidative stress in tumor cells, particularly characterized by a significant increase in hydroxyl radicals and superoxide radicals, which cause substantial damage to the structure and function of cells, ultimately leading to cell apoptosis. Intriguingly, O provided by CaO can degrade VPQDs slowly, and the degradation product, phosphate, as well as CaO-generated calcium ions, can promote tumor calcification. Antitumor immune activation and less metastasis are also observed in VPCaNPs administrated animals. In conclusion, our study unveils the anti-tumor activity of VPQDs as catalysts for generating cytotoxic ROS and the degradation products can promote tumor calcification, providing a promising strategy for treating tumors.
尽管纳米催化医学在肿瘤治疗中已展现出其优势，但其效果在很大程度上依赖于底物浓度，且代谢途径仍不明确。我们发现，紫色磷量子点（VPQDs）无需外部刺激即可催化活性氧（ROS）的产生，并且通过计算模拟和实验证实催化底物为氧气（O）和过氧化氢（HO）。考虑到肿瘤部位O和HO的短缺，我们利用过氧化钙（CaO）为VPQDs提供催化底物，并与它们一起构建纳米颗粒，命名为VPCaNPs。VPCaNPs可在肿瘤细胞中诱导氧化应激，其特征尤其表现为羟基自由基和超氧自由基显著增加，这会对细胞的结构和功能造成实质性损害，最终导致细胞凋亡。有趣的是，CaO提供的O可缓慢降解VPQDs，其降解产物磷酸盐以及CaO产生的钙离子可促进肿瘤钙化。在给予VPCaNPs的动物中还观察到抗肿瘤免疫激活和较少的转移。总之，我们的研究揭示了VPQDs作为产生细胞毒性ROS的催化剂的抗肿瘤活性，且其降解产物可促进肿瘤钙化，为肿瘤治疗提供了一种有前景的策略。
