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Biomimetic gold nano-modulator for deep-tumor NIR-II photothermal immunotherapy via gaseous microenvironment
Honglin Huang1, Zhengxin Xie1, Ningxi Li1
1Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, and School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, P. R. China.
Introduction:
Effective immunotherapeutic treatment of solid tumors has been greatly challenged by the complex hostile tumor immunosuppressive microenvironment (TIME), which typically involves hypoxia and immunosuppression.
Methods:
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.
Results:
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.
Conclusions:
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.
