Immunotherapy represents a promising therapeutic strategy for cancer treatment, but its clinical applications are currently hindered by insufficient therapeutic potency, nonspecific delivery, and adverse side effects. Herein, a novel near‐infrared II (NIR‐II) photo‐triggered plasmonic hyperthermia immunomodulator (RP@IR‐pcNS@HA nanoparticles (NPs)) for anticancer treatment of both primary and distant cancers is reported. This immunomodulator comprises an IR‐1061 dye‐encoded NIR‐II porous cubic AuAg nanoshell (pcNS) loaded with a Toll‐like receptor 7 agonist – R837 in phase change materials (PCMs), further modified with hyaluronic acid (HA). In response to NIR‐II photoirradiation, the RP@IR‐pcNS@HA NPs controllably deliver and release R837 to tumor sites, subsequently perform plasmonic hyperthermia therapy for direct ablation of primary tumors, and elicit robust anticancer immune responses. It is demonstrated that upon NIR‐II irradiation, such a plasmonic hyperthermia immunomodulator combined with anti‐programmed death 1 antibody (αPD‐1) completely eradicates both primary and distant cancers. In addition, this combination treatment successfully elicits robust immune memory responses for effective suppression of recurrence and distant metastasis of cancer. With the excellent NIR‐II surface‐enhanced Raman scattering (SERS) detection ability, the RP@IR‐pcNS@HA NPs combined with αPD‐1 represent an efficient way to develop high‐performance theranostic agents for SERS‐guided combination cancer photoimmunotherapy.

中文翻译：

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用于 SERS 引导的联合癌症免疫治疗的近红外 II 光触发多功能等离子体热疗免疫调节剂


免疫疗法是一种很有前途的癌症治疗策略，但其临床应用目前受到治疗效力不足、非特异性递送和不良副作用的阻碍。在此，报道了一种新型近红外 II （NIR-II） 光触发等离子体热疗免疫调节剂 （RP@IR-pcNS@HA 纳米颗粒 （NPs）），用于原发性和远处癌症的抗癌治疗。该免疫调节剂包括一个 IR-1061 染料编码的 NIR-II 多孔立方 AuAg 纳米壳 （pcNS），该纳米壳在相变材料 （PCM） 中加载了 Toll 样受体 7 激动剂 – R837，并进一步用透明质酸 （HA） 修饰。在 NIR-II 光照射下，RP@IR-pcNS@HA NP 可控地将 R837 输送和释放到肿瘤部位，随后进行等离子体热疗以直接消融原发性肿瘤，并引发强大的抗癌免疫反应。结果表明，在 NIR-II 照射下，这种等离子体热疗免疫调节剂与抗程序性死亡 1 抗体 （αPD-1） 相结合可完全根除原发性和远处癌症。此外，这种联合治疗成功地引发了强大的免疫记忆反应，从而有效抑制癌症的复发和远处转移。凭借出色的 NIR-II 表面增强拉曼散射 （SERS） 检测能力，RP@IR-pcNS@HA NPs 与 αPD-1 相结合，代表了为 SERS 引导的联合癌症光免疫疗法开发高性能治疗诊断剂的有效方法。