Citation: Mei Cong, Guangling Xu, Shaoyou Yang, Jing Zhang, Wenzheng Zhang, Dinesh Dhumal, Erik Laurini, Kaiyue Zhang, Yi Xia, Sabrina Pricl, Ling Peng, Weidong Zhao. A self-assembling prodrug nanosystem to enhance metabolic stability and anticancer activity of gemcitabine[J]. Chinese Chemical Letters, ;2022, 33(5): 2481-2485. doi: 10.1016/j.cclet.2021.11.083 shu

A self-assembling prodrug nanosystem to enhance metabolic stability and anticancer activity of gemcitabine

Mei Cong ^a ,
Guangling Xu ^{b, c} ,
Shaoyou Yang ^a ,
Jing Zhang ^{b, c} ,
Wenzheng Zhang ^{d, e} ,
Dinesh Dhumal ^d ,
Erik Laurini ^f ,
Kaiyue Zhang ^d ,
Yi Xia ^e ,
Sabrina Pricl ^{f, g} ,
Ling Peng ^{d, *,} ,
Weidong Zhao ^{b, c, **,}

a.
School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China
b.
Henan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China
c.
Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China
d.
Aix-Marseille Université, CNRS, Center Interdisciplinaire de Nanoscience de Marseille, UMR 7325, Equipe Labellisé par La Ligue, Marseille 13288, France
e.
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China
f.
Molecular Biology and Nanotechnology Laboratory, Department of Engineering and Architecture, University of Trieste, Trieste 34127, Italy
g.
Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz 90-236, Poland

ling.peng@univ-amu.fr

141051@xxmu.edu.cn

Received Date: 4 July 2021
Revised Date: 28 November 2021
Accepted Date: 28 November 2021
Available Online: 3 December 2021

Figures(5)

Self-assembly is a powerful approach in molecular engineering for biomedical applications, in particular for creating self-assembling prodrugs. Here, we report a self-assembling prodrug of the anticancer drug gemcitabine (Gem) based on amphiphilic dendrimer approach. The prodrug reported in this study demonstrates high drug loading (40%) and robust ability to self-assemble into small nanomicelles, which increase the metabolic stability of Gem and enable entry into cells via endocytosis, hence bypassing transport-mediated uptake. In addition, this prodrug nanosystem exhibited an effective pH- and enzyme-responsive release of Gem, resulting in enhanced anticancer activity and reduced toxicity. Harboring advantageous features of both prodrug- and nanotechnology-based drug delivery, this self-assembling Gem prodrug nanosystem constitutes a promising anticancer candidate. This study also offers new perspectives of the amphiphilic dendrimer nanoplatforms for the development of self-assembling prodrugs.
- Self-assembling prodrug,
- Gemcitabine,
- Amphiphilic dendrimer,
- Anticancer candidate,
- Nanomicelles
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