Covalent binding of 5-tetradecyloxy-2-furoic acid (TOFA) and c(RGDfK) and its co-delivery with Lipusu, a novel synergistic strategy to inhibit the proliferation of nasopharyngeal cancer

Min Feng; Wei Gong; Xin Zhu; Juan Zhu; Junjie Hu; Weihua Xu; Zhichao Ma; Shengmiao Fu; Xinping Chen

doi:10.1016/j.ejps.2025.107092

Covalent binding of 5-tetradecyloxy-2-furoic acid (TOFA) and c(RGDfK) and its co-delivery with Lipusu, a novel synergistic strategy to inhibit the proliferation of nasopharyngeal cancer

Eur J Pharm Sci. 2025 Apr 12:209:107092. doi: 10.1016/j.ejps.2025.107092. Online ahead of print.

Authors

Min Feng¹, Wei Gong¹, Xin Zhu², Juan Zhu³, Junjie Hu⁴, Weihua Xu⁵, Zhichao Ma⁴, Shengmiao Fu⁶, Xinping Chen⁷

Affiliations

¹ College of Life Sciences and Pharmacy, Hainan University, Haikou, Hainan, PR China; Department of Medical Laboratory, Hainan Cancer Hospital, Affiliated Cancer Hospital of Hainan Medical University, Haikou, Hainan, PR China.
² College of Life Sciences and Pharmacy, Hainan University, Haikou, Hainan, PR China.
³ Department of Pathology, Yancheng City Dafeng People's Hospital, Yanchen, Jiangsu, PR China.
⁴ Department of Medical Laboratory, Hainan Cancer Hospital, Affiliated Cancer Hospital of Hainan Medical University, Haikou, Hainan, PR China.
⁵ Department of Medical Laboratory, Hainan Cancer Hospital, Affiliated Cancer Hospital of Hainan Medical University, Haikou, Hainan, PR China; Hainan Tropical Cancer Research Institute, Haikou, Hainan, PR China.
⁶ Hainan Lvtou Medical Laboratory Center, Haikou, Hainan, PR China. Electronic address: fusm58@126.com.
⁷ College of Life Sciences and Pharmacy, Hainan University, Haikou, Hainan, PR China; Department of Medical Laboratory, Hainan Cancer Hospital, Affiliated Cancer Hospital of Hainan Medical University, Haikou, Hainan, PR China; Hainan Tropical Cancer Research Institute, Haikou, Hainan, PR China. Electronic address: chenxinping52@126.com.

PMID: 40228725
DOI: 10.1016/j.ejps.2025.107092

Abstract

As the world's only commercially available paclitaxel liposome, Lipusu (Lip) has been clinically used in chemotherapy for >20 years, but the design concept of Lip remains largely unchanged since its initial development. Based on the study of Acetyl-CoA-carboxylase 1 (ACC1) in nasopharyngeal carcinoma (NPC), we proposed the concept of next-generation liposomes (NGL) utilizing lipid demand balance. In this study, we evaluated the feasibility of ACC1 and integrin α_Vβ₃ as NPC targets, and designed 10 conjugates of 5-tetradecyloxy-2-furoic acid (TOFA) and c(RGDfK) that can bind to Lip. Considering the results of chemical parameter prediction, molecular docking, molecular dynamics simulation (MD) and other aspects, we finally selected and synthesized the compound F, and successfully constructed F-Lip by simple incubation method. Compared with Lip, F-Lip showed stronger toxicity in both HONE-1 cells and corresponding tumor-bearing mice. In conclusion, by regulating the balance of lipid demand, the toxicity of Lip can be improved so as to achieve the goal of inhibiting the proliferation of NPC. This study provides a new model for the future design and development of Lip.

Keywords: Lipusu; Nasopharyngeal cancer; TOFA; c(RGDfK).