基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
包裹过氧化铜和吉西他滨的可生物降解聚合物胶束用于靶向化学免疫治疗
英文原题：Biodegradable polymersomes encapsulating copper peroxide and gemcitabine for targeted chemoimmunotherapy.
查看英文原题
Biodegradable polymersomes encapsulating copper peroxide and gemcitabine for targeted chemoimmunotherapy.
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中文摘要
在此，我们设计了一种可生物降解、ROS响应性聚合物囊泡（HA-PGC），包裹吉西他滨（GEM）和过氧化铜纳米颗粒（CuO₂），并用透明质酸（HA）功能化以靶向CD44过表达的TNBC细胞。到达酸性TME后，CuO₂分解生成过氧化氢（H₂O₂）和Cu²⁺离子，通过基于Cu的类Fenton反应触发强烈的ROS产生。升高的ROS同时抑制胞苷脱氨酶（CDA），增强GEM活化，并消耗谷胱甘肽（GSH），减少ROS清除。诱导的氧化应激进一步促进免疫原性细胞死亡（ICD），促进树突状细胞成熟并增强TIL（肿瘤浸润淋巴细胞）。因此，HA-PGC纳米颗粒有效将冷肿瘤转化为热肿瘤，显著提高抗PD-L1免疫治疗疗效。我们展示了一种新型多功能纳米颗粒平台，结合化学动力学治疗和免疫治疗，为克服三阴性乳腺癌治疗中的耐药性提供了一种有前景的策略，并指导未来智能免疫治疗系统的设计。
展开英文摘要原文
Herein, we engineered biodegradable, ROS-responsive polymersomes (HA-PGC) encapsulating gemcitabine (GEM) and copper peroxide nanoparticles (CuO₂), functionalized with hyaluronic acid (HA) to target CD44-overexpressing TNBC cells. Upon reaching the acidic TME, CuO₂ decomposes to generate hydrogen peroxide (H₂O₂) and Cu 2+ ions, triggering robust ROS production via a Cu-based Fenton-like reaction.
Elevated ROS simultaneously suppresses cytidine deaminase (CDA), enhancing GEM activation, and depletes glutathione (GSH), reducing ROS scavenging. The induced oxidative stress further promotes immunogenic cell death (ICD), facilitating dendritic cell maturation and enhancing tumor-infiltrating lymphocytes. Consequently, HA-PGC nanoparticles effectively convert cold tumors into hot tumors, significantly improving anti-PD-L1 immunotherapy efficacy.
We demonstrated a novel, multifunctional nanoparticle platform combining chemodynamic therapy and immunotherapy, presenting a promising strategy to overcome resistance in triple-negative breast cancer treatment and guide future intelligent immunotherapeutic system design.
论文信息
- 作者
- Lee ML、Jiang W、Chen JCH、Cheng WW、Poon EN、Kwan HY、Li HW
- 第一作者单位
- Department of Chemistry, The Chinese University of Hong Kong, Hong Kong, China.Hong Kong
- 通讯作者单位
- Department of Chemistry, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: hungwingli@cuhk.edu.hk.Hong Kong
- 文献类型
- 非美国政府资助研究
- 期刊
- Journal of controlled release : official journal of the Controlled Release Society2026 May 10
- 原文标识
- PubMed 41780685 · DOI 10.1016/j.jconrel.2026.114772