Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Department of Pharmacology, School of Medicine & Holistic Integrative Medicine, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Biomaterials. 2021 Dec;279:121233. doi: 10.1016/j.biomaterials.2021.121233. Epub 2021 Oct 29.
Photothermal therapy (PTT) is a promising strategy for the treatment of advanced malignant neoplasm. However, the anti-tumor efficacy by PTT alone is insufficient to control tumor growth and metastasis. Here, we report a multifunctional nanotherapeutic system exerting a combined PTT and immunotherapy to synergistically enhance the therapeutic effect on melanoma. In particular, we selected the semiconductor nanomaterial copper sulfide (CuS), which served not only as a near-infrared (NIR) light-triggered photothermal converter for tumor hyperthermia but as a basic carrier to modify Cas9 ribonucleoprotein targeting PTPN2 on its surface. Efficient PTPN2 depletion was observed after the treatment of CuS-RNP@PEI nanoparticles, which caused the accumulation of intratumoral infiltrating CD8 T lymphocytes in tumor-bearing mice and upregulated the expression levels of IFN-ᵧ and TNF-α in tumor tissue, thus sensitizing tumors to immunotherapy. In addition, the effect worked synergistically with tumor ablation and immunogenic cell death (ICD) induced by PTT to amplify anti-tumor efficacy. Taken together, this exogenously controlled method provides a simple and effective treatment option for advanced malignant neoplasm.
光热疗法（PTT）是治疗晚期恶性肿瘤的一种很有前途的策略。然而，单独使用 PTT 的抗肿瘤疗效不足以控制肿瘤生长和转移。在这里，我们报告了一种多功能纳米治疗系统，它采用 PTT 和免疫疗法的联合作用，协同增强对黑色素瘤的治疗效果。具体来说，我们选择了半导体纳米材料硫化铜（CuS），它不仅可以作为近红外（NIR）光触发的光热转换剂，用于肿瘤升温，而且还可以作为基本载体来修饰 Cas9 核糖核蛋白，使其靶向表面的 PTPN2。在用 CuS-RNP@PEI 纳米颗粒治疗后，观察到 PTPN2 的有效耗竭，这导致肿瘤内浸润的 CD8 T 淋巴细胞在荷瘤小鼠中的积聚，并上调肿瘤组织中 IFN-ᵧ和 TNF-α的表达水平，从而使肿瘤对免疫治疗敏感。此外，该效果与 PTT 诱导的肿瘤消融和免疫原性细胞死亡（ICD）协同作用，放大了抗肿瘤疗效。总之，这种外源性控制方法为晚期恶性肿瘤提供了一种简单有效的治疗选择。
