Citation: Lurong Zhang, Xin Wang, Xuan Li, Minglong Huang, Bowen Zhang, Shengyao Xu, Jialin Xing, Yafan Xiao, Yi Zheng, Zhenzhen Zhao, Jin Sun, Zhonggui He, Lingxiao Li, Bingjun Sun. Fine-tuning PEGylation: Leveraging the self-assembly stability and targeting efficiency of biotinylated-paclitaxel prodrug nanoassemblies[J]. Chinese Chemical Letters, ;2026, 37(7): 111694. doi: 10.1016/j.cclet.2025.111694 shu

Fine-tuning PEGylation: Leveraging the self-assembly stability and targeting efficiency of biotinylated-paclitaxel prodrug nanoassemblies

Lurong Zhang ^{a, 1} ,
Xin Wang ^{b, 1} ,
Xuan Li ^a ,
Minglong Huang ^a ,
Bowen Zhang ^a ,
Shengyao Xu ^a ,
Jialin Xing ^a ,
Yafan Xiao ^a ,
Yi Zheng ^a ,
Zhenzhen Zhao ^c ,
Jin Sun ^{a, d} ,
Zhonggui He ^{a, d} ,
Lingxiao Li ^{a, *,} ,
Bingjun Sun ^{a, d, *,}

a.
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
b.
School of Pharmacy, Hainan Medical University, Haikou 571199, China
c.
Department of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China
d.
Joint International Research Laboratory of Intelligent Drug Delivery Systems, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China

xllbinbin@163.com

sunbingjun_spy@sina.com

Received Date: 23 May 2025
Revised Date: 2 August 2025
Accepted Date: 8 August 2025
Available Online: 9 August 2025

Figures(4)

Prodrug nanoassemblies (NPs) have attracted much attention in improving the selectivity of chemotherapy drugs, while most of them suffer from poor targeting efficiency. Biotin, a well-known tumor-targeting ligand, can greatly enhance tumor accumulation. Herein, we construct the biotinylated prodrug (Biotin-PTX) by connecting paclitaxel (PTX) to biotin via a disulfide bond, enabling the prodrug to self-assemble into nanoparticles (Biotin-PTX NPs). However, the pure NPs are observed to be rapidly cleared without polyethylene glycol (PEG) modifying, while excessive PEG can compromise their targeting efficiency, suggesting that it is crucial to optimize the amount of PEG. On this basis, the effect of distearoyl phosphatidylethanolamine-polyethylene glycol₂₀₀₀ (DSPE-PEG_2k) ratios (0%, 5%, 10%, 20%, 40% and 60%, W_PEG/W_prodrug+PEG) on their performance have been investigated. The results provide evidence that Biotin-PTX NPs containing 20% DSPE-PEG_2k (20% NPs) can significantly improve colloidal stability and tumor-targeting efficiency. Moreover, 20% NPs exhibits good antitumor efficacy and safety compared with Taxol, Abraxane and Prodrug Sol. This work highlights the key role of moderate PEGylation in regulating the therapeutic performance of targeting NPs, offering a new way of thinking for tumor-targeting treatment.
- Biotin,
- Prodrug,
- PEGylation,
- Disulfide bond,
- Tumor-targeting
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沈阳化工大学材料科学与工程学院沈阳 110142