Zhang Yingying, Xing Yujuan, Zhou Hong, Ma Enhui, Xu Wenbei, Zhang Xinran, Jiang Canran, Ye Shuo, Deng Yanjia, Wang Hong, Li Jingjing, Zheng Shaohui
School of Medical Imaging, Xuzhou Medical University, Xuzhou, 221004, PR China.
School of Chemical Engineering & Technology, China University of Mining and Technology, Xuzhou, 221116, PR China.
Acta Biomater. 2024 Dec;190:463-475. doi: 10.1016/j.actbio.2024.10.040. Epub 2024 Oct 26.
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.
基于纳米颗粒的光免疫疗法已成为一种有吸引力的消除肿瘤和激活宿主免疫反应的策略。然而，治疗效果受到肿瘤低穿透性和免疫抑制性肿瘤微环境（TME）的严重限制。在此，我们提出了近红外激光（NIR）驱动的Janus纳米马达，用于实现肿瘤深部穿透、光热肿瘤消融和光热触发的增强免疫疗法。Janus纳米马达（AuNR/PMO@CPG）由金纳米棒（AuNR）和周期性介孔有机硅纳米球（PMO）构建而成，随后负载免疫佐剂（CPG ODNs）。在近红外辐射下，纳米马达表现出优异的光热效应，其产生的主动运动速度为19.3 µm/s，可实现肿瘤深部穿透和在体内的积累。此外，良好的光热加热也有利于有效的光热消融，从而触发免疫原性细胞死亡（ICD）。随后，ICD效应促进了肿瘤相关抗原（TAAs）和损伤相关分子模式（DAMPs）的释放，并进一步原位产生大量肿瘤疫苗，与CPG ODNs联合对免疫抑制性TME进行重编程以抑制肿瘤生长。结果，通过将光热疗法诱导的ICD与免疫抑制性TME的调节相结合，在荷CT26小鼠体内实现了显著的协同治疗效果。因此，我们认为合成的纳米马达可为增强肿瘤免疫疗法中光热疗法诱导的ICD提供新的研究方向。重要性声明：基于纳米颗粒的协同光免疫疗法已成为一种流行的消除肿瘤和激活宿主免疫反应的策略。然而，治疗效果受到肿瘤低穿透性和免疫抑制性肿瘤微环境（TME）的严重限制。在这项工作中，我们提出了近红外激光（NIR）驱动的Janus纳米马达，用于实现肿瘤深部穿透、光热肿瘤消融和光热触发的增强免疫疗法。在近红外辐射下纳米马达表现出优异的光热效应，产生主动运动以实现肿瘤深部穿透和在体内的积累。此外，良好的光热加热也有助于有效的光热消融以触发免疫原性细胞死亡（ICD），促进肿瘤相关抗原和损伤相关分子模式（DAMPs）的释放，并进一步原位产生大量肿瘤疫苗，对免疫抑制性TME进行重编程以抑制肿瘤生长。
