Deng Chao, Zhang Qiang, Guo Jiakun, Zhao Xiaofei, Zhong Zhiyuan
Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China.
Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China.
Adv Drug Deliv Rev. 2020;160:199-211. doi: 10.1016/j.addr.2020.10.019. Epub 2020 Oct 31.
Nanomedicines based on synthetic polypeptides are among the most versatile and advanced platforms for tumor therapy. Notably, several polypeptide-based nanodrugs are currently under human clinical assessments. The previous (pre)clinical studies clearly show that dynamic stability (i.e. stable in circulation while destabilized in tumor) of nanomedicines plays a vital role in their anti-tumor performance. Various strategies have recently been developed to design dynamically stabilized polypeptide-based nanomedicines by e.g. crosslinking the nanovehicles with acid, reactive oxygen species (ROS), glutathione (GSH), or photo-sensitive linkers, inter-crosslinking between vehicles and drugs, introducing π-π stacking or lipid-lipid interactions in the nanovehicles, chemically conjugating drugs to vehicles, and forming unimolecular micelles. Interestingly, these robust and smart nanodrugs have demonstrated improved tumor targetability, anti-tumor efficacy, as well as safety profiles in different tumor models. In this review, representative strategies to robust and smart polypeptide-based nanomedicines for targeted treatment of varying malignancies are highlighted. The exciting development of dynamic nanomedicines will foresee further increasing clinical translation in the future.
基于合成多肽的纳米药物是肿瘤治疗中最具通用性和先进性的平台之一。值得注意的是，目前有几种基于多肽的纳米药物正在进行人体临床试验评估。先前的临床前研究清楚地表明，纳米药物的动态稳定性（即在循环中稳定而在肿瘤中不稳定）在其抗肿瘤性能中起着至关重要的作用。最近已经开发出各种策略来设计动态稳定的基于多肽的纳米药物，例如通过用酸、活性氧（ROS）、谷胱甘肽（GSH）或光敏连接剂交联纳米载体，在载体和药物之间进行交联，在纳米载体中引入π-π堆积或脂质-脂质相互作用，将药物化学偶联到载体上，以及形成单分子胶束。有趣的是，这些强大而智能的纳米药物在不同的肿瘤模型中已经显示出改善的肿瘤靶向性、抗肿瘤疗效以及安全性。在这篇综述中，重点介绍了用于靶向治疗各种恶性肿瘤的强大而智能的基于多肽的纳米药物的代表性策略。动态纳米药物令人兴奋的发展预示着未来临床转化将进一步增加。
