仿生金纳米调节剂通过气态微环境重塑策略用于深部肿瘤 NIR-II 光热免疫治疗

Herein, a multifunctional biomimetic gold nano-modulator (denoted as GNR-SNO@MMT) was developed to realize the efficient second near-infrared (NIR-II) photothermal immunotherapy via tumor targeting and deep penetration, vascular normalization and immune reprogramming. NIR-II photothermal agent gold nanorods (GNR) were grafted with thermosensitive S-nitrosothiol (SNO) donors and camouflaged with the tumor-penetrating peptide tLyp-1-modified macrophage membrane (MM) to yield GNR-SNO@MMT.

The engineered membrane coating increased the capacity for tumor inflammatory tropism and deep penetration, which aided GNR-SNO@MMT in ablating tumors together with NIR-II laser irradiation. Moreover, hyperthermia-stimulated nitric oxide (NO) release in situ acted as a gas immunomodulator to effectively enhance blood perfusion and reprogram the TIME via multiple functions (e.g., decreasing PD-L1, repolarizing tumor-associated macrophages, and revitalizing cytotoxic T cells). Ultimately, the inhibition rate against 4T1 mouse mammary tumor model mediated by GNR-SNO@MMT plus NIR-II laser was 94.7% together with 2.4-fold CD8 + T cells infiltrated into tumors than that of the untreated counterpart.

The engineered biomimetic nano-modulator of GNR-SNO@MMT provides an effective and novel photoimmunotherapy candidate against deep-sited solid tumors through immune reconfiguration via NO-involved nanomedicine and external NIR-II laser assistance.