Zhang Lu, Wu Yi, Yin Xingbin, Zhu Zheng, Rojalin Tatu, Xiao Wenwu, Zhang Dalin, Huang Yanyu, Li Longmeng, Baehr Christopher M, Yu Xingjian, Ajena Yousif, Li Yuanpei, Wang Lei, Lam Kit S
Department of Biochemistry & Molecular Medicine, UC Davis NCI-designated Comprehensive Cancer Center, University of California Davis, Sacramento, California 95817, United States.
Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
ACS Nano. 2021 Jan 26;15(1):468-479. doi: 10.1021/acsnano.0c05065. Epub 2020 Dec 17.
To be clinically efficacious, nanotherapeutic drugs need to reach disease tissues reliably and cause limited side effects to normal organs and tissues. Here, we report a proof-of-concept study on the development of a smart peptidic nanophototherapeutic agent in line with clinical requirements, which can transform its morphology from nanoparticles to nanofibrils at the tumor sites. This in vivo receptor-mediated transformation process resulted in the formation and prolonged tumor-retention of highly ordered (J-aggregate type of photosensitizer) photosensitive peptide nanofibrillar network with greatly enhanced photothermal and photodynamic properties. This strategy of "multiple daily low-intensity laser radiation after each intravenous injection of significantly low-dose of nanomaterials" demonstrated effective elimination of 4T1 orthotopic syngeneic breast cancer in mice. The technology for nanomaterial modulation based on living cell surface receptors, in this case tumor-associated αβ integrin, has great potential for clinical translation and is expected to improve the therapeutic efficacy against many cancers.
为了在临床上有效，纳米治疗药物需要可靠地到达病变组织，并对正常器官和组织产生有限的副作用。在此，我们报告了一项符合临床要求的智能肽纳米光治疗剂开发的概念验证研究，该制剂可在肿瘤部位将其形态从纳米颗粒转变为纳米纤维。这种体内受体介导的转变过程导致形成并延长了具有高度增强的光热和光动力特性的高度有序（光敏剂的J-聚集体类型）光敏肽纳米纤维网络在肿瘤中的滞留。“每次静脉注射极低剂量纳米材料后进行多次每日低强度激光照射”的策略证明可有效消除小鼠体内的4T1原位同基因乳腺癌。基于活细胞表面受体（在此为肿瘤相关的αβ整合素）的纳米材料调控技术具有很大的临床转化潜力，有望提高对多种癌症的治疗效果。
