Tumor Receptor-Mediated In Vivo Modulation of the Morphology, Phototherapeutic Properties, and Pharmacokinetics of Smart Nanomaterials.
Tumor Receptor-Mediated In Vivo Modulation of the Morphology, Phototherapeutic Properties, and Pharmacokinetics of Smart Nanomaterials.
复制标题
肿瘤受体介导的智能纳米材料形态、光疗特性和药代动力学的体内调节。
DOI：
10.1021/acsnano.0c05065
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发表时间：
2021
期刊：
影响因子：
17.1
通讯作者：
Lam,KitS
中科院分区：
文献类型：
--
作者：
Zhang,Lu;Wu,Yi;Yin,Xingbin;Zhu,Zheng;Rojalin,Tatu;Xiao,Wenwu;Zhang,Dalin;Huang,Yanyu;Li,Longmeng;Baehr,ChristopherM;Yu,Xingjian;Ajena,Yousif;Li,Yuanpei;Wang,Lei;Lam,KitS
为了在临床上有效，纳米药物需要可靠地到达疾病组织，并对正常器官和组织造成有限的副作用。在这里，我们报告了一项关于开发符合临床要求的智能肽纳米光治疗剂的概念验证研究，该药物可以将其形态从纳米颗粒转变为肿瘤部位的纳米纤维。这种体内受体介导的转化过程导致高度有序（J-聚集体类型的光敏剂）光敏肽纳米纤维网络的形成和延长的肿瘤保留，其具有大大增强的光热和光动力学性质。这种“在每次静脉注射显著低剂量的纳米材料后每天多次低强度激光辐射”的策略证明了小鼠中4 T1原位同基因乳腺癌的有效消除。基于活细胞表面受体的纳米材料调节技术，在这种情况下是肿瘤相关的α3β 1整合素，具有巨大的临床转化潜力，预计将提高对许多癌症的治疗效果。
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 α3β1integrin, has great potential for clinical translation and is expected to improve the therapeutic efficacy against many cancers.