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用于乳腺癌治疗中协同光热化疗和增强免疫治疗的多功能介孔聚多巴胺纳米平台。

Multifunctional mesoporous polydopamine nanoplatforms for synergistic photothermal-chemotherapy and enhanced immunotherapy in breast cancer treatment.

作者信息

Wu Siqiong, Chen Yongjun, Wang Ke, Huang Mingquan, Yang Liuxuan, Yang Jing, Wei Qiming, Tao Chao, Li Chunhong, Zhou Meiling

机构信息

Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China; Department of Pharmacy, Xianning Hospital of Traditional Chinese Medicine, Xianning, Hubei 437100, China.

Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China.

出版信息

Colloids Surf B Biointerfaces. 2025 Apr;248:114483. doi: 10.1016/j.colsurfb.2024.114483. Epub 2024 Dec 27.

DOI:10.1016/j.colsurfb.2024.114483
PMID:39740488
Abstract

Breast cancer remains one of the most prevalent and deadly cancers among women worldwide, necessitating the development of more effective and comprehensive treatment strategies. In this study, we successfully synthesized mesoporous polydopamine (MPDA) with photothermal effects for the co-delivery of the chemotherapeutic drug doxorubicin (DOX) and the immune adjuvant imiquimod (R837), resulting in the development of a multifunctional nanoplatforms termed MDR. MDR displayed excellent photothermal conversion efficiency and pH-responsive drug release behavior. In vitro assessments revealed significant cytotoxicity of MDR against 4T1 cells under 808 nm laser irradiation, with enhanced cellular uptake in both 4T1 cells and bone marrow-derived dendritic cells (BMDCs). Additionally, the expression levels of the costimulatory molecules CD80 and CD86 were remarkably higher in the MDR-treated group than free R837 after co-incubation with immature BMDCs, indicating a stronger ability to promote BMDC maturation and effectively stimulate immune response activation. Intratumoral injection in breast cancer-bearing mice further demonstrated that the MDR + NIR group significantly inhibited tumor growth compared to other groups, with no apparent side effects. In conclusion, the multifunctional nanoplatforms integrating photothermal therapy, chemotherapy, and immunotherapy are expected to provide a novel therapeutic approach for the multimodal treatment of breast cancer.

摘要

乳腺癌仍然是全球女性中最常见且致命的癌症之一,因此需要开发更有效、更全面的治疗策略。在本研究中,我们成功合成了具有光热效应的介孔聚多巴胺(MPDA),用于共递送化疗药物阿霉素(DOX)和免疫佐剂咪喹莫特(R837),从而开发出一种称为MDR的多功能纳米平台。MDR表现出优异的光热转换效率和pH响应性药物释放行为。体外评估显示,在808 nm激光照射下,MDR对4T1细胞具有显著的细胞毒性,并且在4T1细胞和骨髓来源的树突状细胞(BMDC)中细胞摄取均有所增强。此外,与未成熟BMDC共孵育后,MDR处理组中共刺激分子CD80和CD86的表达水平明显高于游离R837,表明其促进BMDC成熟和有效刺激免疫反应激活的能力更强。在荷乳腺癌小鼠体内进行瘤内注射进一步证明,与其他组相比,MDR +近红外(NIR)组显著抑制肿瘤生长,且无明显副作用。总之,整合光热疗法、化疗和免疫疗法的多功能纳米平台有望为乳腺癌的多模式治疗提供一种新的治疗方法。

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