通过在近红外二区生物窗口伪装基于金的光热纳米颗粒以模拟T细胞来产生针对癌症的免疫记忆。

Generating Immunological Memory Against Cancer by Camouflaging Gold-Based Photothermal Nanoparticles in NIR-II Biowindow for Mimicking T-Cells.

作者信息

Xiong Xuefan, Zhang Ying, Huang Xinqi, Zhang Shusheng, Li Qiong

机构信息

Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, School of Chemistry and Chemical Engineering, Linyi University, Linyi, 276005, P. R. China.

Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, College of Medicine, Linyi University, Linyi, 276005, P. R. China.

出版信息

Small. 2024 Dec;20(51):e2407038. doi: 10.1002/smll.202407038. Epub 2024 Oct 12.

Abstract

Photothermal therapy (PTT) against cancer not only directly ablates tumors but also induces tumor immunogenic cell death (ICD). However, the antitumor immune response elicited by ICD is insufficient to prevent relapse and metastasis because of the immunosuppressive tumor microenvironment (TME). A biomimetic nanoplatform (bmNP) mimicking cytotoxic lymphocytes (CTLs) for combinational photothermal-immunotherapy to effectively regulate the immunosuppressive TME is reported here. The bmNP is constructed by wrapping the T-cell membrane onto a new type of photothermal agents, spherical Au-based PNCs (sAuPNCs). Similar to T-cells, the bmNP enhanced accumulation at the tumor site by targeting the tumor via adhesion proteins on T-cell membrane. The obtained sAuPNCs have a wide absorption band in the second near-infrared (NIR-II) region with a high photothermal conversion efficiency (PCE) up to about 75% and excellent photostability. The bmNP with a smaller size is more superior compete with T-cells to bond with tumor cells via PD-1/PD-L1 interaction to effectively block the PD-1 checkpoint of T-cells for preventing T-cell exhaustion. Furthermore, in vivo studies reveal the immunological memory effect is significantly elicited in mice received bmNPs therapy. Collectively, bmNPs show great potential in photothermal-enhanced immunotherapy.

摘要

用于对抗癌症的光热疗法(PTT)不仅能直接消融肿瘤,还能诱导肿瘤免疫原性细胞死亡(ICD)。然而,由于免疫抑制性肿瘤微环境(TME),ICD引发的抗肿瘤免疫反应不足以预防复发和转移。本文报道了一种模仿细胞毒性淋巴细胞(CTL)的仿生纳米平台(bmNP),用于联合光热免疫疗法以有效调节免疫抑制性TME。bmNP是通过将T细胞膜包裹在一种新型光热剂——球形金基等离子体纳米复合材料(sAuPNCs)上构建而成。与T细胞类似,bmNP通过T细胞膜上的黏附蛋白靶向肿瘤,从而增强在肿瘤部位的聚集。所制备的sAuPNCs在第二近红外(NIR-II)区域具有宽吸收带,光热转换效率(PCE)高达约75%,且具有优异的光稳定性。尺寸较小的bmNP更具优势,可通过PD-1/PD-L1相互作用与T细胞竞争结合肿瘤细胞,从而有效阻断T细胞的PD-1检查点以防止T细胞耗竭。此外,体内研究表明,接受bmNP治疗的小鼠体内显著引发了免疫记忆效应。总的来说,bmNP在光热增强免疫疗法中显示出巨大潜力。

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