NIR-activated Janus nanomotors with promoted tumor permeability for synergistic photo-immunotherapy

Abstract

Nanoparticle-based photo-immunotherapy has become an attractive strategy to eliminate tumors and activate host immune responses. However, the therapeutic efficacy is heavily restricted by low tumoral penetration and immunosuppressive tumor microenvironment (TME). Herein, near infrared laser (NIR)-propelled Janus nanomotors were presented for deep tumoral penetration, photothermal tumor ablation and photothermal-triggered augmented immunotherapy. The Janus nanomotors (AuNR/PMO@CPG) were constructed with gold nanorods (AuNR) and periodic mesoporous organo-silica nanospheres (PMO), followed by loading of immune adjuvant (CPG ODNs). Under NIR irradiation, the nanomotors exhibited superior photothermal effect, which produced active motion with a speed of 19.3 µm/s for deep tumor penetration and accumulation in vivo. Moreover, the good photothermal heating also benefited effective photothermal ablation to trigger immunogenic cell death (ICD). Subsequently, the ICD effect promoted the release of tumor-associated antigens (TAAs) and damage associated molecular patterns (DAMPs), and further generated abundant tumor vaccines in situ for reprograming the immunosuppressive TME in combination with CPG ODNs to inhibit tumor growth. As a result, a notable in vivo synergistic therapeutic effect was realized on CT26-bearing mice by combining photothermal therapy-induced ICD with modulation of immunosuppressive TME. Thus, we believe that the synthesized nanomotors can provide a new inspect to boost photothermal therapy-induced ICD in tumor immunotherapy.

Statement of Significance

Nanoparticle-based synergistic photo-immunotherapy has become a popular strategy to eliminate tumors and activate host immune responses. However, the therapeutic efficacy is heavily restricted by low tumoral penetration and immunosuppressive tumor microenvironment (TME). In this work, near infrared laser (NIR)-propelled Janus nanomotors were presented for deep tumoral penetration, photothermal tumor ablation and photothermal-triggered augmented immunotherapy. Under NIR irradiation, the nanomotors exhibited a superior photothermal effect, which produced active motion for deep tumor penetration and accumulation in vivo. Moreover, good photothermal heating also facilitated effective photothermal ablation to trigger immunogenic cell death (ICD), which promoted the release of tumor-associated antigens and damage-associated molecular patterns (DAMPs), and further generated abundant tumor vaccines in situ for reprograming the immunosuppressive TME to inhibit tumor growth.