近日，中山大学巢晖团队研究了窄带隙铱（III）-C₃N₅纳米复合物作为缺氧肿瘤声动力免疫治疗的氧气自给压电声敏剂。该研究于2025年4月28日发表在《美国化学会志》上。

免疫原性低和免疫细胞浸润不足是影响黑色素瘤免疫治疗疗效的主要因素。基于压电材料的超声触发声动力疗法（SDT）因其高效的压电催化产生活性氧（ROS）以诱导免疫原性细胞死亡（ICD）而引起了广泛关注。然而，实体瘤中的缺氧环境阻碍了免疫细胞的浸润，限制了SDT的作用。研究组构建了一种新型的Ir-C₃N₅纳米复合物，该复合物使用富氮氮化碳（C₃N₅）纳米片作为纳米配体，Ir（tpy）Cl₃作为前体。 

新形成的Ir-C₃N₅纳米复合物显示出变窄的带隙和增大的偶极矩，导致更好的电子-空穴对分离和带弯曲，从而在超声波激活时导致ROS爆发。此外，Ir（III）使C₃N₅纳米片能够催化H₂O₂降解为O₂，缓解肿瘤缺氧并增强SDT疗效。从机制上讲，由于压电催化产生ROS，Ir-C₃N₅可以靶向溶酶体，引发溶酶体破裂引起的自噬抑制，并引发焦亡。更重要的是，Ir-C₃N₅激活的切割胱天蛋白酶-1/GSDMD-N焦亡途径与ICD有关，有效地启动了身体的先天性和适应性免疫，以抑制肿瘤转移和复发。

附：英文原文

Title: Narrow-Bandgap Iridium(III)-C3N5 Nanocomplex as an Oxygen Self-Sufficient Piezo-Sonosensitizer for Hypoxic Tumor Sonodynamic Immunotherapy

Author: Xianbo Wu, Jinzhe Liang, Jun Shu, Zeqi Li, Tiantian Yin, Xiting Zhang, Hui Chao

Issue&Volume: April 28, 2025

Abstract: Low immunogenicity and insufficient infiltration of immune cells are the main factors affecting the therapeutic efficacy of melanoma immunotherapy. Ultrasound-triggered sonodynamic therapy (SDT) based on piezoelectric materials has attracted substantial attention due to its high efficiency of piezoelectric catalytic generation of reactive oxygen species (ROS) to induce immunogenic cell death (ICD). However, the hypoxic environment in solid tumors hinders the infiltration of immune cells and limits the SDT effect. Herein, we construct a novel Ir-C3N5 nanocomplex that uses nitrogen-rich carbon nitride (C3N5) nanosheets as nanoligands and Ir(tpy)Cl3 as a precursor. The newly formed Ir-C3N5 nanocomplex exhibits a narrowed band gap and an enlarged dipole moment, resulting in a better electron–hole pair separation and band bending, contributing to the ROS burst upon ultrasonic activation. In addition, Ir(III) enables the C3N5 nanosheets to catalyze the degradation of H2O2 to O2, alleviating tumor hypoxia and reinforcing SDT efficacy. Mechanistically, due to the generation of ROS by piezoelectric catalysis, Ir-C3N5 can target lysosomes to trigger autophagy inhibition caused by lysosome rupture and to evoke pyroptosis. More importantly, the cleaved caspase-1/GSDMD-N pyroptosis pathway activated by Ir-C3N5 was associated with ICD, effectively initiating the innate and adaptive immunity of the body for suppressing tumor metastasis and relapse.

DOI: 10.1021/jacs.5c00843

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.5c00843