Citation: Yaqi Li, Yixin Sun, Qinglong Yan, Wenjing Wang, Shuo Wang, Qing Wang, Danping Wang, Jun Yuan, Jin Sun, Zhonggui He, Zhenbao Li, Bingjun Sun. Redox-triggered prodrug nanoassemblies with high tumor selectivity and biocompatibility break through antitumor dilemma of paclitaxel[J]. Chinese Chemical Letters, ;2026, 37(5): 111350. doi: 10.1016/j.cclet.2025.111350 shu

Redox-triggered prodrug nanoassemblies with high tumor selectivity and biocompatibility break through antitumor dilemma of paclitaxel

Yaqi Li ^{a, 1} ,
Yixin Sun ^{a, 1} ,
Qinglong Yan ^a ,
Wenjing Wang ^a ,
Shuo Wang ^a ,
Qing Wang ^a ,
Danping Wang ^a ,
Jun Yuan ^a ,
Jin Sun ^{a, c} ,
Zhonggui He ^{a, c} ,
Zhenbao Li ^{b, *,} ,
Bingjun Sun ^{a, c, *,}

a.
Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
b.
College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China
c.
Joint International Research Laboratory of Intelligent Drug Delivery Systems, Ministry of Education, Shenyang 110016, China

lizhenbao@ahtcm.edu.cn

sunbingjun_spy@sina.com

Received Date: 26 February 2025
Revised Date: 17 May 2025
Accepted Date: 19 May 2025
Available Online: 20 May 2025

Figures(4)

The advent of the most representative commercially available formulations of paclitaxel, Taxol and Abraxane^®, resolved the intravenous challenge of paclitaxel by increasing the water solubility. However, the severe excipient-related toxicity and poor stability of Taxol, along with the low drug loading (10%), complex preparation processes, and poor tumor selectivity of Abraxane^®, present significant clinical dilemma. To overcome the challenges, 16-methylheptadecanoic acid (16-MH), with excellent biocompatibility was selected as the assembly module. The paclitaxel-16-MH prodrug nanoassemblies (PSSMH NPs) were constructed by conjugating 16-MH with redox-sensitive disulfide bonds and paclitaxel through an ethylene glycol. PSSMH NPs featured the advantages of easy preparation, high drug loading (> 50%) and superior stability (stable storage for 60 days at 25 ℃). Notably, the area under the concentration−time curve (AUC_{0–24 h}) of PSSMH NPs was 14.95-fold compared with Taxol, indicating a significant improvement in the in vivo fate of paclitaxel. Moreover, the existence of redox-sensitive disulfide bonds endowed PSSMH NPs with increased tumor selectivity, resulting in exceptional tolerance and antitumor efficacy. Overall, the redox-triggered prodrug nano-system with high tumor selectivity and biocompatibility exhibits substantial potential for clinical translation.
- Prodrug nanoassemblies,
- Paclitaxel,
- Redox-triggered,
- Tumor selectivity,
- Biocompatibility,
- 16-Methylheptadecanoic acid
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