Citation: Wenfeng Zang, Yixin Sun, Jingyi Zhang, Yanzhong Hao, Qianhui Jin, Hongying Xiao, Zuo Zhang, Xianbao Shi, Jin Sun, Zhonggui He, Cong Luo, Bingjun Sun. Two-tailed modification module tuned steric-hindrance effect enabling high therapeutic efficacy of paclitaxel prodrug nanoassemblies[J]. Chinese Chemical Letters, ;2025, 36(5): 110230. doi: 10.1016/j.cclet.2024.110230 shu

Two-tailed modification module tuned steric-hindrance effect enabling high therapeutic efficacy of paclitaxel prodrug nanoassemblies

Wenfeng Zang ^{a, 1} ,
Yixin Sun ^{a, 1} ,
Jingyi Zhang ^a ,
Yanzhong Hao ^a ,
Qianhui Jin ^a ,
Hongying Xiao ^a ,
Zuo Zhang ^a ,
Xianbao Shi ^b ,
Jin Sun ^{a, c} ,
Zhonggui He ^{a, c} ,
Cong Luo ^{a, c, *,} ,
Bingjun Sun ^{a, c, *,}

a.
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
b.
Department of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China
c.
Joint International Research Laboratory of Intelligent Drug Delivery Systems, Ministry of Education, Shenyang 110016, China

luocong@syphu.edu.cn

sunbingjun_spy@sina.com

Received Date: 22 May 2024
Revised Date: 6 July 2024
Accepted Date: 8 July 2024
Available Online: 8 July 2024

Figures(5)

Self-assembled prodrug nanomedicine has emerged as an advanced platform for antitumor therapy, mainly comprise drug modules, response modules and modification modules. However, existing studies usually compare the differences between single types of modification modules, neglecting the impact of steric-hindrance effect caused by chemical structure. Herein, single-tailed modification module with low-steric-hindrance effect and two-tailed modification module with high-steric-hindrance effect were selected to construct paclitaxel prodrugs (P-LA_C18 and P-BA_C18), and the in-depth insights of the steric-hindrance effect on prodrug nanoassemblies were explored. Notably, the size stability of the two-tailed prodrugs was enhanced due to improved intermolecular interactions and steric hindrance. Single-tailed prodrug nanoassemblies were more susceptible to attack by redox agents, showing faster drug release and stronger antitumor efficacy, but with poorer safety. In contrast, two-tailed prodrug nanoassemblies exhibited significant advantages in terms of pharmacokinetics, tumor accumulation and safety due to the good size stability, thus ensuring equivalent antitumor efficacy at tolerance dose. These findings highlighted the critical role of steric-hindrance effect of the modification module in regulating the structure-activity relationship of prodrug nanoassemblies and proposed new perspectives into the precise design of self-assembled prodrugs for high-performance cancer therapeutics.
- Prodrug nanoassemblies,
- Two-tailed modification module,
- Steric-hindrance,
- Paclitaxel,
- Anticancer
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1.
沈阳化工大学材料科学与工程学院沈阳 110142