Tumor Receptor-Mediated In Vivo Modulation of the Morphology, Phototherapeutic Properties, and Pharmacokinetics of Smart Nanomaterials

• Published in: ACS nano 2021-01, Vol.15 (1), p.468-479
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Animals; Cell Line, Tumor; Mice; Nanoparticles; Photochemotherapy; Photosensitizing Agents - pharmacology
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.0c05065

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 α3β1 integrin, has great potential for clinical translation and is expected to improve the therapeutic efficacy against many cancers.