Huang Guoqin, Zhang Lianying, Feng Jiahao, Wu Dan, Wu Libo, Pan Weilun, Jiang Yu, Chen Ming, Chen Jinxiang, Shui Pixian
School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China.
Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, and Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Small. 2025 Feb;21(7):e2407553. doi: 10.1002/smll.202407553. Epub 2025 Jan 10.
Covalent organic frameworks (COFs), known for their exceptional in situ encapsulation and precise release capabilities, are emerging as pioneering drug delivery systems. This study introduces a hypoxia-responsive COF designed to encapsulate the chemotherapy drug gambogic acid (GA) in situ. Bimetallic gold-palladium islands were grown on UiO-66-NH (UiO) to form UiO@Au-Pd (UAPi), which were encapsulated with GA through COF membrane formation, resulting in a core-shell structure (UAPiGC). Further modification with hyaluronic acid (HA) created UiO@Au-Pd@GA-COF@HA (UAPiGCH) for enhanced tumor targeting. In the hypoxic tumor microenvironment, the COF collapses, releasing GA and UAPi, initiating a triple therapeutic response: nanozyme-catalyzed therapy, near-infrared II (NIR-II) mild photothermal therapy (mild-PTT), and chemotherapy. UAPi exhibits catalase (CAT)-like and peroxidase (POD)-like activities, generating oxygen to alleviate hypoxia and reactive oxygen species (ROS) for tumor destruction. GA acts as a chemotherapeutic agent and inhibits heat shock protein 90 (HSP90), enhancing photothermal sensitivity. In vitro and in vivo studies confirm UAPiGCH's ability to induce pyroptosis, stimulate dendritic cell maturation, and boost T cell infiltration, demonstrating its potential as a precise therapeutic nanoplatform. This strategy integrates multiple therapies into a hypoxia-responsive system, offering promising applications in cancer treatment.
共价有机框架（COFs）以其出色的原位封装和精确释放能力而闻名，正成为开创性的药物递送系统。本研究介绍了一种缺氧响应性COF，旨在原位封装化疗药物藤黄酸（GA）。在UiO-66-NH（UiO）上生长双金属金-钯岛以形成UiO@Au-Pd（UAPi），通过形成COF膜将GA封装在其中，形成核壳结构（UAPiGC）。用透明质酸（HA）进一步修饰得到UiO@Au-Pd@GA-COF@HA（UAPiGCH）以增强肿瘤靶向性。在缺氧的肿瘤微环境中，COF坍塌，释放GA和UAPi，引发三重治疗反应：纳米酶催化治疗、近红外II（NIR-II）温和光热治疗（温和PTT）和化疗。UAPi表现出类似过氧化氢酶（CAT）和过氧化物酶（POD）的活性，产生氧气以缓解缺氧并产生活性氧（ROS）用于肿瘤破坏。GA作为化疗药物，抑制热休克蛋白90（HSP90），增强光热敏感性。体外和体内研究证实UAPiGCH能够诱导细胞焦亡、刺激树突状细胞成熟并促进T细胞浸润，证明其作为精确治疗纳米平台的潜力。该策略将多种疗法整合到缺氧响应系统中，在癌症治疗中具有广阔的应用前景。
