A Near‐Infrared II Photo‐Triggered Multifunctional Plasmonic Hyperthermia Immunomodulator for SERS‐Guided Combination Cancer Immunotherapy

Abstract 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.