Citation: Haijiao Li, Mingzu Zhang, Jinlin He, Jian Liu, Xingwei Sun, Peihong Ni. Synthesis of curcumin polyprodrug via click chemistry and construction of dual-drug-loaded nano platform for highly efficient tumor treatment[J]. Chinese Chemical Letters, ;2025, 36(8): 110615. doi: 10.1016/j.cclet.2024.110615 shu

Synthesis of curcumin polyprodrug via click chemistry and construction of dual-drug-loaded nano platform for highly efficient tumor treatment

Haijiao Li ^a ,
Mingzu Zhang ^a ,
Jinlin He ^a ,
Jian Liu ^b ,
Xingwei Sun ^{c, *,} ,
Peihong Ni ^{a, *,}

a.
College of Chemistry, Chemical Engineering and Materials Science, State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, Suzhou Key Laboratory of Macromolecular Design and Precision Synthesis, Soochow University, Suzhou 215123, China
b.
Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, China
c.
Intervention Department, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China

sdfeysxw@163.com

phni@suda.edu.cn

Received Date: 23 July 2024
Revised Date: 29 October 2024
Accepted Date: 5 November 2024
Available Online: 6 November 2024

Figures(5)

Micellar nanostructures formed by amphiphilic polymers are prone to dissociation when the in vivo environment changes. Polyprodrug micelles can cross-link with other hydrophobic drugs through non-covalent bonds, which has the advantage of fixed structure and avoids the use of chemical cross-linking agents. In this study, we prepared a polyprodrug with hydrophobic curcumin (CUR) and hydrophilic poly(ethylene glycol) (PEG) in the main chain through a click reaction between CUR derivatives containing azide groups and di-alkynly-capped PEG. Due to the presence of benzene rings in the structure of CUR, the polyprodrug can form non-covalent cross-linked nanoparticles (NCCL-CUR NPs) through hydrophobic and π-π stacking interaction. The structure, molecular weight, and self-assembly properties of the polyprodrug were characterized. The anti-cancer drug camptothecin (CPT) was encapsulated in the polyprodrug nanoparticles, producing dual-drug-loaded nanoparticles (abbreviated as CPT@NCCL-CUR NPs). The test results indicate that the NPs have reductive responsiveness and can release the original drugs CUR and CPT in phosphate buffer (PB) solution containing glutathione (GSH), while remaining stability in physiological environment. Cell and in vivo experiments further demonstrate that the dual-drug-loaded CPT@NCCL-CUR NPs can inhibit the growth of tumor through synergistic effects. This work provides a valuable approach for the preparation of amphiphilic polyprodrug with anti-tumor CUR as the backbone, and the stable dual-drug-loaded NPs containing both CUR and CPT through non-covalent cross-linking for synergistic therapy.
- Click reaction,
- Polyprodrug,
- Non-covalent cross-linking,
- Stimuli responsiveness,
- Synergistic therapy,
- Curcumin,
- Camptothecin
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