Li Lin-Song, Chen Peng-Wei, Zhao Xue-Jie, Cheng Dong, Liu Bang-Bang, Tang Xian-Jiao, Zhu Wen-Qi, Yang Xiaojing, Zhao Mei-Xia
Henan Key Laboratory of Natural Medicine Innovation and Transformation, Henan University, Kaifeng 475004, China; State Key Laboratory of Antiviral Drugs, Henan University, Kaifeng 475004, China.
Henan Key Laboratory of Natural Medicine Innovation and Transformation, Henan University, Kaifeng 475004, China; State Key Laboratory of Antiviral Drugs, Henan University, Kaifeng 475004, China; The Zhongzhou Laboratory for Integrative Biology, Henan University, Kaifeng, China.
J Colloid Interface Sci. 2025 Feb 15;680(Pt A):202-214. doi: 10.1016/j.jcis.2024.11.003. Epub 2024 Nov 2.
Smart nanoplatforms designed for nuclear-targeted delivery of chemotherapeutic agents to tumor sites are pivotal in advancing tumor treatment and immunotherapy. Herein, we introduced a novel nuclear-targeting double-shell smart nanoplatform (HMCuS/Pt/ICG@MnO@9R-P201 (HMCPIM9P)), which synergistically enhances chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), immunotherapy and chemodynamic therapy (CDT). The core of this nanoplatform consists of double-shell multifunctional nanoparticles (HMCuS@MnO) that enable targeted delivery of the photosensitizer Indocyanine Green (ICG) and the chemotherapeutic agent cisplatin (Pt). By effectively consuming glutathione (GSH), these nanoparticles boost the chemotherapeutic efficacy of Pt. Additionally, the manganese ion (Mn) present activate the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) (cGAS-STING) pathway, bolstering adaptive immune responses against tumors and elevating the level of tumor-infiltrating CD8+ T cells. The incorporation of the hepatoma-targeting peptide (9R-P201 peptide) allows the system to exhibit FOXM1 receptor-mediated nuclear targeting properties specifically in hepatocellular carcinoma (HCC). Notably, when combined with near-infrared (NIR) light, HMCPIM9P demonstrated a remarkable tumor inhibition rate of 95.6 %, fostered a robust immune response, and significantly inhibited tumor growth and recurrence. Overall, the smart nanoplatform boasts active nuclear targeting capabilities, enabling the enrichment of chemotherapeutic agents at tumor sites, and holds great potential for synergistic applications in enhancing chemotherapy and immunotherapy for HCC.
设计用于将化疗药物核靶向递送至肿瘤部位的智能纳米平台在推进肿瘤治疗和免疫治疗方面至关重要。在此,我们介绍了一种新型的核靶向双壳智能纳米平台(HMCuS/Pt/ICG@MnO@9R-P201(HMCPIM9P)),它能协同增强化疗、光动力疗法(PDT)、光热疗法(PTT)、免疫疗法和化学动力疗法(CDT)。该纳米平台的核心由双壳多功能纳米颗粒(HMCuS@MnO)组成,其能够实现光敏剂吲哚菁绿(ICG)和化疗药物顺铂(Pt)的靶向递送。通过有效消耗谷胱甘肽(GSH),这些纳米颗粒提高了Pt的化疗效果。此外,存在的锰离子(Mn)激活环鸟苷酸 - 腺苷酸合成酶(cGAS)-干扰素基因刺激物(STING)(cGAS-STING)途径,增强针对肿瘤的适应性免疫反应并提高肿瘤浸润性CD8 + T细胞水平。肝癌靶向肽(9R-P201肽)的掺入使该系统在肝细胞癌(HCC)中特别表现出FOXM1受体介导的核靶向特性。值得注意的是,当与近红外(NIR)光结合时,HMCPIM9P表现出95.6%的显著肿瘤抑制率,促进了强大的免疫反应,并显著抑制肿瘤生长和复发。总体而言,该智能纳米平台具有主动核靶向能力,能够使化疗药物在肿瘤部位富集,在增强肝癌化疗和免疫治疗的协同应用方面具有巨大潜力。
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