免疫检查点阻断(ICB)治疗,虽然在各种癌症中显示出希望,由于肿瘤的免疫抑制微环境(TME)和与免疫细胞浸润相关的挑战,在肝癌中表现出有限的有效性。努力将“冷”TME转变为“发炎”状态,特别是通过化学免疫疗法,由于它们具有诱导免疫原性细胞死亡和增强细胞毒性T淋巴细胞(CTL)浸润的潜力,因此引起了人们的兴趣。尽管如此,化疗免疫疗法的疗效往往受到次优药代动力学的影响,肿瘤积聚不良,和脱靶毒性。在这里,作为回应,我们介绍一个创新的,更温和的热治疗方法利用具有中孔的金纳米框架靶向递送免疫刺激咪喹莫特和NIR-II光热治疗。该策略采用靶向分子修饰以确保精确的肿瘤靶向,由光声成像引导。在温和的热处理之后,有免疫原性蛋白(CRT和HSP90)的释放,增强肿瘤免疫原性。在咪喹莫特的协助下,发生大量CTL浸润,伴有促炎因子释放(TNF-α,IL-6),将M2巨噬细胞转化为M1表型。最终,拟议的策略结合了PD-L1/PD-1封锁,咪喹莫特和温和的热处理,以协同增强肿瘤的免疫原性,改造TME,抑制肝癌,ICB协同免疫热疗法取得进展。
Immune checkpoint blockade (ICB) therapy, while showing promise in various cancers, exhibits limited effectiveness in hepatic carcinoma due to the tumor\'s immunosuppressive microenvironment (TME) and challenges associated with immune cell infiltration. Efforts to transform the \"cold\" TME into an \"inflamed\" state, notably through chemo-immunotherapy, have sparked interest due to their potential to induce immunogenic cell death and augment the infiltration of cytotoxic T lymphocytes (CTLs). Nonetheless, the efficacy of chemo-immunotherapy is often compromised by suboptimal pharmacokinetics, poor tumor accumulation, and off-target toxicity. Herein, in response, we introduce an innovative, milder thermal therapeutic approach leveraging gold nano frameworks with mesopores for the targeted delivery of the immunostimulant
imiquimod and NIR-II photothermal therapy. This strategy employs targeted molecule modifications to ensure precise tumor targeting, guided by photoacoustic imaging. Subsequent to mild thermal treatment, there is a release of immunogenic proteins (CRT and HSP90), enhancing tumor immunogenicity. Assisted by
imiquimod, substantial CTL infiltration occurs, accompanied by pro-inflammatory factor release (TNF-α, IL-6), transforming M2 macrophages into the M1 phenotype. Ultimately, the proposed strategy combines PD-L1/PD-1 blockade,
imiquimod and mild thermal treatment to synergistically enhance tumor immunogenicity, remodel the TME, and restrain hepatic carcinoma, making strides in ICB synergistic immune-thermal therapy.