Luo Xuan, Jiao Qishu, Pei Shicheng, Zhou Shuyao, Zheng Yaxin, Shao Weiyang, Xu Keming, Zhong Wenying
Department of Chemistry, China Pharmaceutical University, Nanjing, 210009, China.
Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing, 210009, China.
Adv Healthc Mater. 2024 Dec;13(30):e2401787. doi: 10.1002/adhm.202401787. Epub 2024 Aug 5.
Type I photodynamic therapy (PDT) generates reactive oxygen species (ROS) through oxygen-independent photoreactions, making it a promising method for treating hypoxic tumors. However, the superoxide anion (O∙) generated usually exhibits a low oxidation capacity, restricting the antitumor efficacy of PDT in clinical practice. Herein, a photoactivated self-assembled nanoreactor (1-NBS@CeO) is designed through integration of type I PDT and cerium oxide (CeO) nanozymes for inducing cascade-amplified oxidative stress in hypoxic tumors. The nanoreactor is constructed though co-assembly of an amphiphilic peptide (1-NBS) and CeO, giving well-dispersed spherical nanoparticles with enhanced superoxide dismutase (SOD)-like and peroxidase (POD)-like activities. Following light irradiation, 1-NBS@CeO undergoes type I photoreactions to generated O∙, which is further catalyzed by the nanoreactors, ultimately forming hypertoxic hydroxyl radical (∙OH) through cascade-amplified reactions. The PDT treatment using 1-NBS@CeO results in elevation of intracellular ROS and depletion of GSH content in A375 cells, thereby inducing mitochondrial dysfunction and triggering apoptosis and ferroptosis of tumor cells. Importantly, intravenous administration of 1-NBS@CeO alongside light irradiation showcases enhances antitumor efficacy and satisfactory biocompatibility in vivo. Together, the self-assembled nanoreactor facilitates cascade-amplified photoreactions for achieving efficacious type I PDT, which holds great promise in developing therapeutic modules towards hypoxic tumors.
I型光动力疗法（PDT）通过不依赖氧气的光反应产生活性氧（ROS），使其成为治疗缺氧肿瘤的一种有前景的方法。然而，通常产生的超氧阴离子（O∙）氧化能力较低，限制了PDT在临床实践中的抗肿瘤疗效。在此，通过整合I型PDT和氧化铈（CeO）纳米酶设计了一种光活化自组装纳米反应器（1-NBS@CeO），用于在缺氧肿瘤中诱导级联放大的氧化应激。该纳米反应器通过两亲性肽（1-NBS）和CeO的共组装构建而成，形成具有增强的超氧化物歧化酶（SOD）样和过氧化物酶（POD）样活性的分散良好的球形纳米颗粒。光照后，1-NBS@CeO发生I型光反应生成O∙，纳米反应器进一步催化O∙，最终通过级联放大反应形成高毒性的羟基自由基（∙OH）。使用1-NBS@CeO进行的PDT治疗导致A375细胞内ROS升高和谷胱甘肽（GSH）含量耗尽，从而诱导线粒体功能障碍并触发肿瘤细胞的凋亡和铁死亡。重要的是，静脉注射1-NBS@CeO并结合光照在体内显示出增强的抗肿瘤疗效和令人满意的生物相容性。总之，这种自组装纳米反应器促进了级联放大的光反应，以实现有效的I型PDT，这在开发针对缺氧肿瘤的治疗模块方面具有巨大潜力。
