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

• Published in: International journal of nanomedicine Vol. 18; pp. 1281 - 1298
• Main Authors: Zhong, Zhi-Xin, Li, Xu-Zhao, Liu, Jin-Tao, Qin, Nan, Duan, Hong-Quan, Duan, Xiao-Chuan
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2023; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: 7-ethyl-10-hydroxycamptothecin; Analysis; Animals; Camptothecin; Cancer; Cancer therapies; Cell Line, Tumor; Chemotherapy; Chromatography; Clinical trials; Computer software industry; Disulfides - chemistry; Drug delivery systems; Drug Delivery Systems - methods; Drug Liberation; Drug therapy; glutathione responsive; Health aspects; Humans; Hydrochloric acid; Irinotecan - pharmacology; nanoassemblies; Nanoparticles; Nanoparticles - chemistry; Original Research; Pancreatic cancer; pancreatic cancer therapy; Pancreatic Neoplasms; Pancreatic Neoplasms - drug therapy; prodrug; Prodrugs - chemistry; Tumors; United States; China; Beijing China; United States > US; prodrug; pancreatic cancer therapy; glutathione responsive; 7-ethyl-10-hydroxycamptothecin; nanoassemblies
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S404848

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.
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.
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.
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.