Carrier-Free, Pure Nanodrug Formed by the Self-Assembly of an Anticancer Drug for Cancer Immune Therapy

• Published in: Molecular pharmaceutics Vol. 15; no. 6; pp. 2466 - 2478
• Main Authors: Fan, Lulu, Zhang, Bingchen, Xu, Aixiao, Shen, Zhichun, Guo, Yan, Zhao, Ruirui, Yao, Huilu, Shao, Jing-Wei
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 04.06.2018
• Subjects: A549 Cells; Animals; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - therapeutic use; Apoptosis - drug effects; Drug Design; Female; Humans; Immunotherapy - methods; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Neoplasms - drug therapy; Neoplasms - immunology; Neoplasms - pathology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Triterpenes - administration & dosage; Triterpenes - chemistry; Triterpenes - therapeutic use; Ursolic Acid; Xenograft Model Antitumor Assays; self-assembly; carrier-free nanodrug; UA NPs; liver protection; immunotherapy
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.8b00444

Ursolic acid (UA) is a food-plant-derived natural product which has good anticancer activities and low toxicity. However, the poor water solubility of UA limits its application in clinic. To address this issue, we developed a carrier-free nanodrug by self-assembly of UA. Here, we showed that UA nanoparticles (NPs) have a near-spherical shape with a diameter of ∼150 nm. UA NPs exhibited higher antiproliferative activity; significantly caused apoptosis; decreased the expression of COX-2/VEGFR2/VEGFA; and increased the immunostimulatory activity of TNF-α, IL-6, and IFN-β and decreased the activity of STAT-3 in A549 cells in vitro. Furthermore, UA NPs could inhibit tumor growth and have the ability of liver protection in vivo. More importantly, UA NPs could significantly improve the activation of CD4+ T-cells, which indicated that UA NPs have the potential for immunotherapy. Overall, a carrier-free UA nanodrug may be a promising drug to further enhance their anticancer efficacy and immune function.