Citation: Chao Liu, Liming Gong, Yanhong Liu, Shuangqing Wang, Hao Wu, Liqing Chen, Mingji Jin, Zhonggao Gao, Wei Huang. Lipoic acid-locked reduction-responsive core-cross-linked micelles delivering paclitaxel for triple-negative breast cancer treatment[J]. Chinese Chemical Letters, ;2025, 36(8): 110570. doi: 10.1016/j.cclet.2024.110570 shu

Lipoic acid-locked reduction-responsive core-cross-linked micelles delivering paclitaxel for triple-negative breast cancer treatment

Chao Liu ^{a, b, c, 1} ,
Liming Gong ^{a, c, 1} ,
Yanhong Liu ^{a, c} ,
Shuangqing Wang ^{a, c} ,
Hao Wu ^{a, c} ,
Liqing Chen ^{a, c} ,
Mingji Jin ^{a, c} ,
Zhonggao Gao ^{a, c, *,} ,
Wei Huang ^{a, c, *,}

a.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
b.
State Key Laboratory of Advanced Medical Materials and Devices, Institute of Biomedical Engineering, Tianjin Institutes of Health Science, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China
c.
Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

zggao@imm.ac.cn

huangwei@imm.ac.cn

Received Date: 12 June 2024
Revised Date: 16 October 2024
Accepted Date: 21 October 2024
Available Online: 22 October 2024

Figures(5)

Most anti-tumor agents suffer from systemic non-specific distribution and low aggregation in tumors, which not only decreases the therapeutic efficacy, but also causes systemic toxic side effects in the treatments of tumors. In recent years, the rapid development of nanotechnology has brought new ideas for the application of anti-tumor drugs. Nanomedicines, such as liposomes and micelles, can improve drug targeting and prolong systemic circulation time to promote anti-tumor efficacy and reduce toxic side effects. However, conventional micelles bear the risk of instability and premature drug leaking in the blood circulation. We designed a reduction-responsive core-cross-linked micelle PTX@Fmoc-LA-PEG efficiently encapsulating Paclitaxel (PTX) via π-π stacking and hydrophobic interactions of Fmoc and PTX. Moreover, the micelle was further locked based on the cross-linking properties of the disulfide bonds formed by lipoic acid (LA). As expected, the core-cross-linked micelles PTX@Fmoc-LA-PEG remained stable in normal physiological environments, while restoring the normal drug release rate of micelles under the highly reducing environment due to LA unlocking. The blank micelles (Fmoc-LA-PEG) exhibited excellent biocompatibility, while the drug-loaded micelles (PTX@Fmoc-LA-PEG) displayed a remarkable anti-tumor effect in vitro and in vivo experiments. These results suggested that core-cross-linked micelles PTX@Fmoc-LA-PEG have great potential to improve the targeting and stability of anti-tumor drugs.
- Core-cross-linked micelles,
- Reduction-responsive,
- Lipoic acid,
- Paclitaxel,
- Triple-negative breast cancer
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沈阳化工大学材料科学与工程学院沈阳 110142