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

Abstract

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.

• Authors: Lu Zhang, Yi Wu, Xingbin Yin, Zheng Zhu, Tatu Rojalin, Wenwu Xiao, Dalin Zhang, Yanyu Huang, Longmeng Li, Christopher M Baehr, Xingjian Yu, Yousif Ajena, Yuanpei Li, Lei Wang, Kit S Lam
• Journal: ACS nano (ACS Nano) Vol. 15 Issue 1 Pg. 468-479 (01 26 2021) ISSN: 1936-086X [Electronic] United States
• PMID: 33332957 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Photosensitizing Agents

Topics

• Animals
• Cell Line, Tumor
• Mice
• Nanoparticles
• Photochemotherapy
• Photosensitizing Agents (pharmacology)