Developing a Novel Indium(III) Agent Based on Human Serum Albumin Nanoparticles: Integrating Bioimaging and Therapy

• Published in: Journal of medicinal chemistry Vol. 65; no. 7; pp. 5392 - 5406
• Main Authors: Zhang, Zhenlei, Yang, Tongfu, Zhang, Juzheng, Li, Wenjuan, Li, Shanhe, Sun, Hongbin, Liang, Hong, Yang, Feng
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 14-04-2022
• Subjects: Cell Line, Tumor; Humans; Indium - pharmacology; Nanoparticles; Phosphatidylinositol 3-Kinases; Serum Albumin, Human - metabolism
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/acs.jmedchem.1c01790

To effectively integrate diagnosis and therapy for tumors, we proposed to develop an indium (In) agent based on the unique property of human serum albumin (HSA) nanoparticles (NPs). A novel In­(III) quinoline-2-formaldehyde thiosemicarbazone compound (C5) was optimized with remarkable cytotoxicity and fluorescence to cancer cells in vitro. An HSA–C5 complex NP delivery system was then successfully constructed. Importantly, the HSA–C5 complex NPs have stronger bioimaging and therapeutic efficiency relative to C5 alone in vivo. Besides, the results of gene chip analysis revealed that C5/HSA–C5 complex NPs act on cancer cells through multiple mechanisms: inducing autophagy, apoptosis, and inhibiting the PI3K–Akt signaling pathway.