Dual-drug loaded hyaluronic acid conjugates coated polydopamine nanodrugs for synergistic chemo-photothermal therapy in triple negative breast cancer

被引：0
作者：
Li, Min [1 ,2 ]
Chu, Kaile [1 ,2 ]
Zhou, Qin [1 ,2 ]
Wang, Hongliang [1 ,2 ]
Zhang, Wenjun [3 ,4 ]
Zhang, Yaqiong [1 ,2 ]
Lv, Junping [1 ,2 ]
Zhou, Haitao [1 ,2 ]
An, Jie [1 ,2 ]
Wu, Zhifang [1 ,2 ]
Li, Sijin [1 ,2 ]
机构：
[1] Shanxi Med Univ, Hosp 1, Dept Nucl Med, Taiyuan 030001, Shanxi, Peoples R China
[2] Shanxi Med Univ, Mol Imaging Precis Med Collaborat Innovat Ctr, Taiyuan 030001, Shanxi, Peoples R China
[3] Dalian Univ Technol, State Key Lab Fine Chem, Dalian 116024, Liaoning, Peoples R China
[4] Dalian Univ Technol, Sch Chem Engn, Panjin 124221, Liaoning, Peoples R China
来源：
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES | 2025年 / 308卷
基金：
中国国家自然科学基金;
关键词：
Dual-drug loading; Hyaluronic acid conjugates; Polydopamine; Synergistic therapy; Breast cancer; MESOPOROUS POLYDOPAMINE; NANOPARTICLES; DELIVERY; CHEMOTHERAPY; PACLITAXEL;
D O I：
10.1016/j.ijbiomac.2025.142559
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Although combination of chemotherapy and photothermal therapy (PTT) holds significant promise for treating triple-negative breast cancer, the existing delivery systems for achieving synergistic antitumor activity remains unsatisfactory. Herein, we developed of dual-drug loaded hyaluronic acid (HA) nanodrugs, which exhibited pH, glutathione (GSH), and thermal triple-responsiveness and CD44-targeting capabilities for chemo-PTT synergistic therapy in breast cancer. Gemcitabine (GCB) and metformin (MET) were conjugated to HA via amide and disulfide bonds to form dual-drug loaded prodrugs (HSGM), which were then coated onto the surface of polydopamine nanoparticles (PDA NPs) to self-assemble into HSGM/PDA NPs. These NPs selectively accumulated at the tumor site through HA receptors and released GCB and MET in response to low pH and high GSH concentrations. The NPs demonstrated excellent photothermal performance, with heat generated from near-infrared (NIR)-laser irradiation accelerating drug release within tumor. Additionally, MET inhibited the production of heat shock protein 70 (HSP 70), mitigating thermotolerance induced by PTT, thereby enhancing the PTT effect. The combination of chemotherapy and PTT synergistically improved anti-tumor efficacy (tumor inhibition ratio: 99.11 %) while showing negligible systemic toxicity, effectively preventing tumor metastasis and recurrence. This integrated approach offers valuable insights for the clinical treatment of breast cancer and other malignant tumors.
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页数：16
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