自化学发光触发的 Ir(III) 络合物光敏剂用于针对缺氧肿瘤的光动力疗法。
Self-Chemiluminescence-Triggered Ir(III) Complex Photosensitizer for Photodynamic Therapy against Hypoxic Tumor.
发表日期:2024 Aug 16
作者:
Shengnan Liu, Haoran Chen, Qi Wu, Yan Sun, Yu Pei, Ziwei Wang, Dongxia Zhu, Gungzhe Li, Martin R Bryce, Yulei Chang
来源:
Cell Death & Disease
摘要:
有限的光学穿透深度和缺氧的肿瘤微环境(TME)是阻碍传统光动力疗法(PDT)实际应用的关键因素。为了从根本上解决这些问题,自发光光敏剂(PS)可以实现高效的PDT。在此,报道了一种自化学发光(CL)触发的 Ir 复合物 PS,即 IrL2,具有低 O2 依赖性 I 型光化学过程,可用于有效的 PDT。合理的设计在H2O2和血红蛋白(Hb)的催化下实现了从共价键合的鲁米诺单元到IrL2中的Ir络合物的高效化学发光共振能量转移(CRET),生成O2·-和1O2。脂质体 IrL2H 纳米颗粒 (NP) 通过负载 IrL2 和 Hb 构建。细胞内的H2O2和负载的Hb催化IrL2H的鲁米诺部分,然后通过CRET激发Ir2部分产生I型和II型活性氧(ROS),即使在缺氧条件下也能诱导细胞死亡,促进细胞凋亡。 IrL2H 用于肿瘤成像,通过瘤内注射无需外部光源即可抑制 4T1 小鼠模型中的肿瘤生长。这项工作为过渡金属配合物 PS 提供了新的设计,克服了 PDT 中外部光源和缺氧 TME 的限制。
The limited optical penetration depth and hypoxic tumor microenvironment (TME) are key factors that hinder the practical applications of conventional photodynamic therapy (PDT). To fundamentally address these issues, self-luminescent photosensitizers (PSs) can achieve efficient PDT. Herein, a self-chemiluminescence (CL)-triggered Ir complex PS, namely, IrL2, with low-O2-dependence type I photochemical processes is reported for efficient PDT. The rational design achieves efficient chemiluminescence resonance energy transfer (CRET) from covalently bonded luminol units to the Ir complex in IrL2 under the catalysis of H2O2 and hemoglobin (Hb) to generate O2•- and 1O2. Liposome IrL2H nanoparticles (NPs) are constructed by loading IrL2 and Hb. The intracellular H2O2 and loaded Hb catalyze the luminol part of IrL2H, and the Ir2 part is then excited to produce types I and II reactive oxygen species (ROS) through CRET, inducing cell death, even under hypoxic conditions, and promoting cell apoptosis. IrL2H is used for tumor imaging and inhibits tumor growth in 4T1-bearing mouse models through intratumoral injection without external light sources. This work provides new designs for transition metal complex PSs that conquer the limitations of external light sources and the hypoxic TME in PDT.