@article{Li2024, 
author = {Guanting Li and Fengli Xia and Hongying Xiao and Shunzhe Zheng and Shuwen Fu and Han Qiao and Qianhui Jin and Xuanbo Zhang and Dun Zhou and Chutong Tian and Jin Sun and Zhonggui He and Bingjun Sun},
title = {Fine-tuning the structure-tolerance-antitumor efficacy axis of prodrug nanoassemblies via branched aliphatic functionalization},
year = {2024},
journal = {Nano Research},
volume = {17},
number = {4},
pages = {2908-2918},
keywords = {self-assembly, antitumor efficacy, 7-ethyl-10-hydroxycamptothecin (SN38), tolerance, prodrug nanoassembly},
url = {https://www.sciopen.com/article/10.1007/s12274-023-6081-4},
doi = {10.1007/s12274-023-6081-4},
abstract = {Small-molecule prodrug nanoassemblies have emerged as efficient antitumor drug delivery systems. However, in the case of camptothecins-based prodrug nanoassemblies, linear aliphatic side chain modification often results in rod-shaped or irregularly shaped nanoassemblies, which are highly unfavorable for sterilization through filtration, and may cause capillary blockage upon intravenous injection. The rational design of camptothecins-based prodrug nanoassemblies remains a challenge. Herein, we propose that branched aliphatic alcohol (BAA) functionalization could fine-tune the structure-tolerance-antitumor efficacy axis of prodrug nanoassemblies. Correspondingly, four SN38-BAA prodrugs were synthesized by conjugating 7-ethyl-10-hydroxycamptothecin (SN38) with BAAs of varying lengths via a tumor redox-responsive disulfide bond, which self-assemble into uniform spherical nanoparticles. The length of BAA was found to significant impact the multiple drug delivery process, including colloidal stability, drug release profiles and pharmacokinetics. Overall, SN38-C21 NPs (SN38-11-heneicosanol nanoparticles), featuring the longest BAA, showcased multiple therapeutic advantages, ultimately culminating the optimal antitumor efficacy and tolerance. The findings underscore the potential of BAA functionalization in strengthening the therapeutic outcomes of prodrug nanoassemblies, and provide valuable insights for developing translational camptothecins-based nanomedicines.}
}