@article{Liang2025, 
author = {Jiaqi Liang and Jiaping Wu and Jianbin Shi and Siyu Wen and Zhixiao Zhang and Jin Sun and Zhonggui He and Cong Luo and Shenwu Zhang},
title = {Fatty chain engineering dictates self-assembly behavior of linker-free artesunate nanoassemblies for optimized antitumor efficacy},
year = {2025},
journal = {Nano Research},
volume = {18},
number = {9},
pages = {94907773},
keywords = {artesunate-fatty alcohol conjugate, small molecule self-assembly, breast cancer therapy},
url = {https://www.sciopen.com/article/10.26599/NR.2025.94907773},
doi = {10.26599/NR.2025.94907773},
abstract = {Emerging evidence has established artesunate (ART) as a potent anticancer candidate, yet its clinical utility remains constrained by rapid clearance and limited bioavailability. To overcome these limitations, we developed fatty chain-driven self-assembling nanoassemblies (NAs) as an innovative therapeutic platform. In contrast to conventional prodrug-based self-assembled nanoassemblies (PBSANs), our ART conjugates (ART-R) activate antitumor effects without requiring responsive modules, substantially streamlining drug design. In this study, we investigated the assembly behavior, stability, and antitumor efficacy of ART-R conjugates with varying side chain lengths: short (ART-C4), medium (ART-C8, ART-C12), and long (ART-C14, ART-C18). To prolong systemic circulation and achieve tumor-selective release, we engineered reduction-responsive sp-ART-R NAs via 2-Distearoyl-sn-glycero-3-phosphoethanolamine-disulfide bond-polyethylene glycol 2000 (DSPE-SS-PEG2K) modification. Following comprehensive evaluation, sp-ART-C14 NAs with the optimal side chain length were selected, which exhibit the most suitable octanol-water partition coefficient (logP), good assembly capability, stability, cytotoxicity, as well as optimal pharmacokinetic behavior and tumor accumulation ability. In the 4T1 breast tumor model, sp-ART-C14 NAs also demonstrated excellent therapeutic efficacy. This study overcomes the limitations of traditional PBSANs, eliminates dependence on response modules, and provides a new drug delivery solution for ART.}
}