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采用负载厚朴酚的介孔聚多巴胺纳米颗粒结合光热效应和低剂量二甲双胍的乳腺癌强化综合治疗

Enhanced integrated therapy for breast cancer employing Honokiol-loaded mesoporous polydopamine nanoparticles in conjunction with photothermal effects and low-dose metformin.

作者信息

Du Qianqian, Zhang Qianfan, Li Jialing, Wang Xiaofei, Gao Xiangyu, Tan Guangyuan, Feng Qian, Li Jigang, Meng Yanchun, Yu Yongsheng

机构信息

Department of Ultrasound Diagnosis, Xiangya Hospital, Central South University, Xiangya Road, Changsha, China.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.

出版信息

APL Bioeng. 2025 Mar 19;9(1):016115. doi: 10.1063/5.0256571. eCollection 2025 Mar.

DOI:10.1063/5.0256571
PMID:40115422
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11925484/
Abstract

Breast cancer remains a significant global health challenge, emphasizing the pressing need for innovative therapeutic approaches. Our thorough research investigates the potential of mesoporous polydopamine nanoparticles (MPDA) as a targeted treatment for breast cancer. Meticulously crafted, these nanoparticles were loaded with honokiol (HK), which is a natural product, and then coated with functionalized hyaluronic acid (HA) to boost their ability to target breast cancer cells that overexpress CD44 receptors. The deep penetrating and photothermal (PTT) composite nanosystem combined with low-dose metformin (Met) improves the efficacy of synergetic therapy against breast tumors. The designed nanosystem exhibited exceptional biocompatibility and stability, suggesting its suitability for therapeutic use. Our studies demonstrated that the nanosystem precisely targeted and penetrated breast cancer cells, resulting in significant cell death. Additionally, studies showed that the nanosystem markedly inhibited tumor growth compared to the control group. This tumor-inhibiting effect was due to the combined action of the encapsulated HK, free Met, and the photothermal effect induced by near-infrared laser irradiation. This combination potently stimulates the expression of cleaved caspase-3 and cleaved PARP proteins, ultimately triggering cell apoptosis and effectively curbing tumor proliferation. Our research not only underscores the promising potential of nanoparticles for targeted breast cancer therapy but also sets the stage for further exploration and development of novel nanomedicine-based therapeutic strategies.

摘要

乳腺癌仍然是一项重大的全球健康挑战,这凸显了对创新治疗方法的迫切需求。我们深入的研究调查了介孔聚多巴胺纳米颗粒(MPDA)作为乳腺癌靶向治疗手段的潜力。这些精心制作的纳米颗粒负载了天然产物厚朴酚(HK),然后用功能化透明质酸(HA)进行包覆,以增强它们靶向过度表达CD44受体的乳腺癌细胞的能力。深度穿透且具有光热(PTT)效应的复合纳米系统与低剂量二甲双胍(Met)相结合,提高了协同治疗乳腺肿瘤的疗效。所设计的纳米系统表现出卓越的生物相容性和稳定性,表明其适用于治疗用途。我们的研究表明,该纳米系统能够精确靶向并穿透乳腺癌细胞,导致显著的细胞死亡。此外,研究显示与对照组相比,该纳米系统能显著抑制肿瘤生长。这种肿瘤抑制作用归因于封装的HK、游离的Met以及近红外激光照射诱导的光热效应的联合作用。这种联合作用有力地刺激了裂解的半胱天冬酶-3和裂解的聚ADP核糖聚合酶蛋白的表达,最终触发细胞凋亡并有效抑制肿瘤增殖。我们的研究不仅强调了纳米颗粒在乳腺癌靶向治疗方面的广阔前景,也为进一步探索和开发基于新型纳米药物的治疗策略奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f518/11925484/857e314ca5e0/ABPID9-000009-016115_1-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f518/11925484/fb4316747b8c/ABPID9-000009-016115_1-g0d1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f518/11925484/e9521d425ab9/ABPID9-000009-016115_1-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f518/11925484/e264961e9242/ABPID9-000009-016115_1-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f518/11925484/e967fb5a97cd/ABPID9-000009-016115_1-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f518/11925484/78e6b6344f92/ABPID9-000009-016115_1-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f518/11925484/fa90e01bd5cd/ABPID9-000009-016115_1-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f518/11925484/91f2dba04f22/ABPID9-000009-016115_1-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f518/11925484/857e314ca5e0/ABPID9-000009-016115_1-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f518/11925484/fb4316747b8c/ABPID9-000009-016115_1-g0d1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f518/11925484/e9521d425ab9/ABPID9-000009-016115_1-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f518/11925484/e264961e9242/ABPID9-000009-016115_1-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f518/11925484/e967fb5a97cd/ABPID9-000009-016115_1-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f518/11925484/78e6b6344f92/ABPID9-000009-016115_1-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f518/11925484/fa90e01bd5cd/ABPID9-000009-016115_1-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f518/11925484/91f2dba04f22/ABPID9-000009-016115_1-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f518/11925484/857e314ca5e0/ABPID9-000009-016115_1-g007.jpg

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