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Research Article | Open Access

Branched module-modified SN38 prodrug nanoassemblies for improved colorectal cancer therapy: Effectively balance efficacy and safety

Qing Wang1,§, Shiyi Zuo1,3,§, Shufang Zheng1, Cuiyun Liu1, Yaqiao Li1, Jiayu Guo1, Danping Wang1, Shuo Wang1, Wenjing Wang1, Bowen Zhang1, Minglong Huang1, Xianbao Shi4, Jin Sun1,2, Zhonggui He1,2, Bingjun Sun1,2 ()
Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
Joint International Research Laboratory of Intelligent Drug Delivery Systems, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China
School of Chemical Engineering, The University of Adelaide, Adelaide, SA 5005, Australia
Department of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China

§ Qing Wang and Shiyi Zuo contributed equally to this work.

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SN38-SS-BAlc18 nanoparticles (NPs), constructed based on the modular design strategy, showed unique advantages in self-assembly capacity, redox responsive drug release, cytotoxicity, in vivo fate, antitumor effect, and biological safety, effectively addressing the limitations of the current Irinotecan and SN38 treatments.

Abstract

The clinical utility of irinotecan is restricted by individual variability in carboxylesterase expression. Direct administration of its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN38), presents an appealing alternative due to its potent anti-tumor efficacy. However, the undesirable properties of SN38, such as poor water solubility and non-target toxicity, present significant hurdles to its clinical development. Prodrug nanoassemblies based on modular design strategy show promise in overcoming these challenges by enhancing drug delivery and selective activation. In modular design, the modification module plays a crucial role in improving the self-assembly capability of prodrugs. While current studies mainly focus on using straight aliphatic chains for prodrug design, branched aliphatic chains emerge as superior alternatives warranting further investigation. In this study, we selected 2-heptylundecanol (BAlc18) as modification module to construct an SN38 prodrug. Through exquisite design, SN38-SS-BAlc18 NPs integrated prominent properties in self-assembly capability, specific activation and biocompatibility, resolving the challenges of irinotecan and SN38, ultimately demonstrating excellent anti-tumor efficacy. This exploration enriched the design theory of prodrug nanoassemblies that can effectively balance safety and colorectal anti-tumor efficacy.

Keywords

irinotecanSN38prodrug nanoassembliesdisulfide bondsbranched aliphatic chains

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Nano Research
Volume 18 Issue 1,
January 2025
Article number: 94907011
DOI: 10.26599/NR.2025.94907011
Cite this article:
Wang Q, Zuo S, Zheng S, et al. Branched module-modified SN38 prodrug nanoassemblies for improved colorectal cancer therapy: Effectively balance efficacy and safety. Nano Research, 2025, 18(1): 94907011. https://doi.org/10.26599/NR.2025.94907011
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