Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, State Key Laboratory of Molecular Nanoscience, Division of Life Science, Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, 999077, China.
Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin, 300071, China.
Adv Sci (Weinh). 2022 Apr;9(10):e2104885. doi: 10.1002/advs.202104885. Epub 2022 Feb 8.
Immunogenic cell death (ICD) through apoptosis or necroptosis is widely adopted to improve the therapeutic effect in cancer treatment by triggering a specific antitumor immunity. However, the tumor resistance to apoptosis/necroptosis seriously impedes the therapeutic effect. Recently, ferroptosis featured with excessive lipid peroxidation is demonstrated capable of bypassing the apoptosis/necroptosis resistance to kill cancer cells. To date, numerous efficient ferroptosis inducers are developed and successfully utilized for sensitizing cancer cells to ferroptosis. Unfortunately, these inducers can hardly generate adequate immunogenicity during induction of ferroptotic cancer cell death, which distinctly attenuates the efficacy of triggering antitumor immune response, therefore leads to unsatisfactory therapeutic effect. Herein, a novel high-performance photothermal nanoparticle (TPA-NDTA NP) is designed by exploiting energy via excited-state intramolecular motion and employed for immensely assisting ferroptosis inducer to evoke highly efficient ICD through ferroptosis pathway. Tumor models with poor immunogenicity are used to demonstrate the tremendously enhanced therapeutic effect endowed by highly enhanced immunogenic ferroptosis in vitro and in vivo by virtue of the NPs. This study sheds new light on a previously unrecognized facet of boosting the immunogenicity of ferroptosis for achieving satisfactory therapeutic effect in cancer therapy.
免疫原性细胞死亡（ICD）通过细胞凋亡或坏死性细胞凋亡广泛用于通过触发特异性抗肿瘤免疫来提高癌症治疗的疗效。然而，肿瘤对细胞凋亡/坏死性细胞凋亡的抵抗严重阻碍了治疗效果。最近，具有过度脂质过氧化的铁死亡被证明能够绕过细胞凋亡/坏死性细胞凋亡抵抗杀死癌细胞。迄今为止，已经开发出许多有效的铁死亡诱导剂，并成功地用于敏化癌细胞对铁死亡的敏感性。不幸的是，这些诱导剂在诱导铁死亡的癌细胞死亡期间几乎不能产生足够的免疫原性，这明显削弱了触发抗肿瘤免疫反应的效果，因此导致治疗效果不佳。在此，通过利用激发态分子内运动产生的能量，设计了一种新型高性能光热纳米粒子（TPA-NDTA NP），并将其用于极大地辅助铁死亡诱导剂通过铁死亡途径引发高效的 ICD。使用免疫原性差的肿瘤模型，证明了通过 NPs 在体外和体内极大地增强了免疫原性铁死亡的高度高效 ICD，从而赋予了极高的治疗效果。这项研究为提高铁死亡的免疫原性以实现癌症治疗中令人满意的治疗效果提供了新的视角。
