Citation: Tingting Li, Yunchu Zhang, Siyao Che, Yuanyuan Zhang, Yin Wu, Weiling Zhuo, Xifeng Zhang, Wanyu Wang, Jiaqi Zheng, Xiang Gao, Yuzhu Hu, Ting Luo. Stimuli-responsive codelivery of apatinib and doxorubicin potentiates chemotherapy efficacy in breast cancer[J]. Chinese Chemical Letters, ;2026, 37(9): 111936. doi: 10.1016/j.cclet.2025.111936 shu

Stimuli-responsive codelivery of apatinib and doxorubicin potentiates chemotherapy efficacy in breast cancer

Tingting Li ^{a, b, 1} ,
Yunchu Zhang ^{a, b, 1} ,
Siyao Che ^{a, b, 1} ,
Yuanyuan Zhang ^{a, d, 1} ,
Yin Wu ^{a, b} ,
Weiling Zhuo ^{a, b} ,
Xifeng Zhang ^{a, b} ,
Wanyu Wang ^{a, b} ,
Jiaqi Zheng ^{a, d} ,
Xiang Gao ^{a, b} ,
Yuzhu Hu ^{a, b, *,} ,
Ting Luo ^{a, c, *,}

a.
Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Medicine, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
b.
Department of Radiation Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Medicine, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
c.
Breast Disease Center, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
d.
West China School of Pharmacy, West China Hospital, Sichuan University, Chengdu 610041, China

huyuzhu023@foxmail.com

luoting@wchscu.cn

Received Date: 25 July 2025
Revised Date: 24 September 2025
Accepted Date: 7 October 2025
Available Online: 8 October 2025

Figures(5)

The escalating incidence of breast cancer threatens to women's health, underscoring the urgent need for the development of new therapies with reduced toxicity and increased efficacy. Combination therapy strategy holds promising potential to improve therapeutic outcomes, however, most chemotherapeutic drugs agents are hindered by poor water solubility and non-specific toxicity. The combination of chemotherapy drugs with targeted therapies represents a reliable approach. In this study, we designed a combination regimen utilizing the chemotherapeutic agent doxorubicin (Dox) alongside the anti-angiogenic drug apatinib (AP) for breast cancer treatment. Methoxy poly(ethylene glycol)-disulfide-poly(lactic acid) (PEG-SS-PLA) and cyclo(Arg-Gly-Asp-D-Tyr-Cys) conjugated PEG-PLA (cRGD-PEG-PLA) were prepared to achieve both reductive response and active targeting for co-delivery of drugs. The self-assembled drug-loaded micelles exhibited an average particle size of 61.50 nm. Our findings indicate that AP significantly enhances Dox uptake in breast cancer cells. Cellular and animal experimental results consistently demonstrated that the AP+Dox/cRGD-m effectively promotes apoptosis of breast cancer cells, while markedly inhibiting tumor growth and pulmonary metastasis. Additionally, AP+Dox/cRGD-m is biodegradable and sustainable, exhibiting a favorable safety profile in vivo. This study suggests that AP+Dox/cRGD-m may have potential clinical application in the treatment of breast cancer.
- Chemotherapy sensitization,
- Stimuli-responsive,
- Apatinib,
- Doxorubicin,
- Breast cancer
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