International Journal of Nanomedicine (Mar 2023)

Disulfide Bond-Based SN38 Prodrug Nanoassemblies with High Drug Loading and Reduction-Triggered Drug Release for Pancreatic Cancer Therapy

  • Zhong ZX,
  • Li XZ,
  • Liu JT,
  • Qin N,
  • Duan HQ,
  • Duan XC

Journal volume & issue
Vol. Volume 18
pp. 1281 – 1298

Abstract

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Zhi-Xin Zhong,1,* Xu-Zhao Li,1,* Jin-Tao Liu,1 Nan Qin,1 Hong-Quan Duan,1– 3 Xiao-Chuan Duan1,4 1School of Pharmacy, Tianjin Medical University, Tianjin, 300070, People’s Republic of China; 2Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, People’s Republic of China; 3Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University, Tianjin, 300070, People’s Republic of China; 4School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, 300070, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong-Quan Duan; Xiao-Chuan Duan, School of Pharmacy, School of Biomedical Engineering and Technology, Tianjin Medical University, 22, Qi Xiang Tai Road, Tianjin, 300070, People’s Republic of China, Tel +86-22-83336680, Fax +86-22-83336560, Email [email protected]; [email protected]: Chemotherapy is a significant and effective therapeutic strategy that is frequently utilized in the treatment of cancer. Small molecular prodrug-based nanoassemblies (SMPDNAs) combine the benefits of both prodrugs and nanomedicine into a single nanoassembly with high drug loading, increased stability, and improved biocompatibility.Methods: In this study, a disulfide bond inserted 7-ethyl-10-hydroxycamptothecin (SN38) prodrug was rationally designed and then used to prepare nanoassemblies (SNSS NAs) that were selectively activated by rich glutathione (GSH) in the tumor site. The characterization of SNSS NAs and the in vitro and in vivo evaluation of their antitumor effect on a pancreatic cancer model were performed.Results: In vitro findings demonstrated that SNSS NAs exhibited GSH-induced SN38 release and cytotoxicity. SNSS NAs have demonstrated a passive targeting effect on tumor tissues, a superior antitumor effect compared to irinotecan (CPT-11), and satisfactory biocompatibility with double dosage treatment.Conclusion: The SNSS NAs developed in this study provide a new method for the preparation of SN38-based nano-delivery systems with improved antitumor effect and biosafety.Graphical Abstract: Keywords: 7-ethyl-10-hydroxycamptothecin, prodrug, nanoassemblies, glutathione responsive, pancreatic cancer therapy

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