Low persistence, metabolic dysfunction in microenvironment, and tumor-derived immunosuppression of Natural killer (NK) cells in patients are greatly limited the successful clinical application of NK cell-based cancer immunotherapy. Interestingly, herein that human serum albumin-encapsulated black phosphorus quantum dots (BPQDs@HSA) can effectively augment antitumor efficacy of clinical patients-derived NK cell immunotherapy is found. As the donor of phosphate group, BPQDs@HSA binds with the protein of phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1A) and activates the downstream PI3K-Akt and mTOR signaling pathways to reprogram cell metabolism of glycolysis and further promote the oxidative phosphorylation, sequentially maintains the cell viability and immunity of NK cells. And multiomics analysis is therefore conducted to reveal the underlying immunoregulation mechanisms, and that BPQDs@HSA can interact with the Toll-like receptor (TLR) on the NK cell surface and increase the expression level of mTOR, and thus activate downstream NF-κB signalling pathways to regulate cytokine secretion and enhance immune tumoricidal is found. BPQDs@HSA can also enhance immune surveillance, relieve immune suppression, and inhibit tumor immune escape. Collectively, this study not only demonstrates a successful strategy for nanomedicine-potentiated immune-cancer therapy, but also sheds light on the understanding of interface between nanomedicine and immune cells activation.

中文翻译：

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黑磷量子点对 NK 细胞进行代谢重编程可增强癌症免疫治疗

自然杀伤（NK）细胞的低持久性、微环境代谢功能障碍以及患者体内肿瘤源性免​​疫抑制极大地限制了基于NK细胞的癌症免疫治疗的成功临床应用。有趣的是，本文发现人血清白蛋白封装的黑磷量子点（BPQDs@HSA）可以有效增强临床患者衍生的NK细胞免疫疗法的抗肿瘤功效。BPQDs@HSA作为磷酸基供体，与磷脂酰肌醇4-磷酸5-激酶1型γ（PIP5K1A）蛋白结合，激活下游PI3K-Akt和mTOR信号通路，重新编程细胞糖酵解代谢，进一步促进糖酵解。氧化磷酸化，依次维持 NK 细胞的细胞活力和免疫力。因此，通过多组学分析揭示了潜在的免疫调节机制，BPQDs@HSA可以与NK细胞表面的Toll样受体（TLR）相互作用，增加mTOR的表达水平，从而激活下游NF - κB发现调节细胞因子分泌和增强免疫杀肿瘤的信号通路。BPQDs@HSA还可以增强免疫监视、解除免疫抑制、抑制肿瘤免疫逃逸。总的来说，这项研究不仅展示了纳米医学增强免疫癌症治疗的成功策略，而且还揭示了纳米医学与免疫细胞激活之间界面的理解。