PDF(Pubmed)
Abstract：
To overcome current limitations in photoimmunotherapy, such as insufficient tumor antigen generation and a subdued immune response, a novel photo-/metallo dual-mode immunotherapeutic agent (PMIA) is introduced for potent near-infrared (NIR) light-triggered cancer therapy. PMIA features a dumbbell-like AuPt heterostructure decorated with starry Pt nanoclusters, meticulously engineered for enhancing plasmonic catalysis through multi-dimensional regulation of Pt growth on Au nanorods. Under NIR laser exposure, end-tipped Pt nanoclusters induce efficient electron-hole spatial separation along the longitudinal axis, resulting in radial and axial electron distribution polarization, conferring unique anisotropic properties to PMIA. Additionally, starry Pt nanoclusters on the sides of Au nanorods augment the local electron enrichment field. Validated through finite-difference time-domain analysis and Raman scattering, this configuration fosters local electron enrichment, facilitating robust reactive oxygen species generation for potent photoimmunotherapy. Moreover, Pt nanoclusters facilitate Pt2+ ion release, instigating intranuclear DNA damage and inducing synergistic immunogenic cell death (ICD) for metalloimmunotherapy. Consequently, PMIA elicits abundant danger-associated molecular patterns, promotes T cell infiltration, and triggers systemic immune responses, effectively treating primary and distant tumors, inhibiting metastasis in vivo. This study unveils a pioneering dual-mode ICD amplification strategy driven by NIR light, synergistically integrating photoimmunotherapy and metalloimmunotherapy, culminating in potent cancer photometalloimmunotherapy.
摘要：
为了克服目前光免疫疗法的局限性，如肿瘤抗原产生不足和免疫反应减弱，引入了一种新型光/金属双模式免疫治疗剂（PMIA），用于有效的近红外（NIR）光触发的癌症治疗。PMIA具有哑铃状的AuPt异质结构，装饰有星状的Pt纳米团簇，精心设计，通过多维调节Au纳米棒上的Pt生长来增强等离子体催化作用。在近红外激光照射下，末端Pt纳米团簇沿纵轴诱导有效的电子-空穴空间分离，导致径向和轴向电子分布极化，赋予PMIA独特的各向异性性能。此外,Au纳米棒侧面的星状Pt纳米团簇增强了局部电子富集场。通过有限差分时域分析和拉曼散射验证，这种配置促进了局部电子富集，促进强大的活性氧产生，用于有效的光免疫疗法。此外，Pt纳米团簇促进Pt2+离子释放，刺激核内DNA损伤并诱导金属免疫疗法的协同免疫原性细胞死亡（ICD）。因此,PMIA引发了丰富的与危险相关的分子模式，促进T细胞浸润，并引发全身免疫反应，有效治疗原发性和远处肿瘤，抑制体内转移。这项研究揭示了一种开创性的由NIR光驱动的双模ICD放大策略，协同整合光免疫疗法和金属免疫疗法，最终导致有效的癌症光免疫治疗。
