Huang Jia-Qi, Zhao Lin-Ping, Zhou Xiang, Liu Ling-Shan, Zheng Rong-Rong, Deng Fu-An, Liu Yi-Bin, Yu Xi-Yong, Li Shi-Ying, Cheng Hong
Department of Pulmonary and Critical Care Medicine Zhujiang Hospital, School of Biomedical Engineering, Southern Medical University, Guangzhou, 510515, P. R. China.
School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, P. R. China.
Small. 2022 Apr;18(15):e2107467. doi: 10.1002/smll.202107467. Epub 2022 Feb 27.
Abnormal tumor metabolism causes the hypoxic microenvironment, which greatly limits the efficacy of photodynamic therapy (PDT). In this work, a strategy of metabolic reprogramming is proposed to economize O for enhanced PDT against hypoxic tumors. The carrier-free O -economizer (designated as LonCe) is prepared based on the metabolic antitumor drug of Lonidamine (Lon) and the photosensitizer of chlorin e6 (Ce6). By virtue of intermolecular interactions, Lon and Ce6 self-assemble into nanosized LonCe with favorable stability and high drug contents. Compared with Ce6, LonCe exhibits an improved cellular uptake and photodynamic property for tumor treatment. Moreover, LonCe is capable of inhibiting cell metabolism and mitochondrial respiration to remit the tumor hypoxia, which would promote reactive oxygen species (ROS) production and elevate the PDT efficacy on tumor suppression. In vivo experiments indicate that intravenously injected LonCe prefers to accumulate at the tumor site for highly efficient PDT regardless of the hypoxic environment. Besides, the self-delivery LonCe is fabricated without any carriers, which avoids the excipients induced system toxicity and immunogenicity in vivo. This carrier-free nanomedicine with cell respiratory inhibition mechanism would expedite the development and clinical translation of photodynamic nanoplatforms in tumor treatment.
肿瘤代谢异常导致缺氧微环境，这极大地限制了光动力疗法（PDT）的疗效。在这项工作中，提出了一种代谢重编程策略，以节省氧气用于增强对缺氧肿瘤的光动力治疗。基于氯尼达明（Lon）的代谢抗肿瘤药物和叶绿素e6（Ce6）的光敏剂制备了无载体氧气节约剂（命名为LonCe）。通过分子间相互作用，Lon和Ce6自组装成具有良好稳定性和高药物含量的纳米级LonCe。与Ce6相比，LonCe在肿瘤治疗中表现出改善的细胞摄取和光动力性能。此外，LonCe能够抑制细胞代谢和线粒体呼吸以缓解肿瘤缺氧，这将促进活性氧（ROS）的产生并提高光动力疗法对肿瘤抑制的疗效。体内实验表明，静脉注射的LonCe无论在缺氧环境下都倾向于在肿瘤部位积累以进行高效光动力治疗。此外，自递送的LonCe是在没有任何载体的情况下制备的，这避免了体内辅料诱导的系统毒性和免疫原性。这种具有细胞呼吸抑制机制的无载体纳米药物将加速光动力纳米平台在肿瘤治疗中的开发和临床转化。
