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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2025 · IF 9.7

Chlorella-based bioactive oxygen generator for sustained tumor hypoxia alleviation and combined-modality tumor therapy

Can Zhang,Shiqi Liu,Yuqing Cao,Weidong Zhang,Yuchu He,Wenkang Tu,Weili Xue,Dawei Gao,Xuwu Zhang

The hypoxic tumor microenvironment (TME) promotes tumor progression and therapeutic resistance primarily through the activation of hypoxia-inducible factor-α (HIF-α). However, current oxygen-sensitizing strategies are hindered by low delivery efficiency, transient efficacy, and severe adverse effects. In this study, we developed a composite system (C@W) comprising Chlorella pyrenoidosa (CHL) and tungsten disulfide (WS₂). This platform synergistically integrates the photosynthetic oxygen generation capacity of CHL with the photocatalytic functionality of WS₂, enabling multimodal antitumor efficacy through hypoxic TME remodeling, photocatalytic therapy, and immune activation. Upon irradiation with 660 nm near-infrared (NIR) light, CHL continuously released oxygen via in situ photosynthesis, thereby suppressing HIF-α expression and alleviating TME hypoxia. Concurrently, WS₂ efficiently catalyzed the conversion of molecular oxygen into cytotoxic singlet oxygen ( 1 O₂). Experimental results demonstrated that this system induced immunogenic cell death (ICD) in tumor cells, promoted dendritic cell maturation via damage-associated molecular pattern (DAMP) release, facilitated M2-to-M1 macrophage polarization, and significantly enhanced tumor-infiltrating CD8 + T cell populations. This bio-inorganic hybrid platform addresses the spatiotemporal limitations of conventional oxygen-enhancing therapies by establishing a dual-engine oxygen self-supply system (photosynthesis–photocatalysis). It synergistically alleviates the immunosuppressive TME while integrating microenvironment regulation with immune activation, thereby offering a novel therapeutic paradigm for solid tumor treatment.

研究领域: 肿瘤学 · 纳米医学 · 光动力治疗 · 肿瘤微环境 · 免疫治疗 · 生物杂化系统 · 光合作用生物学
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