Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People's Republic of China.
Chongqing Key Laboratory of Ultrasound Molecular Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People's Republic of China.
J Nanobiotechnology. 2022 Nov 3;20(1):468. doi: 10.1186/s12951-022-01682-5.
The hypoimmunogenicity of tumors is one of the main bottlenecks of cancer immunotherapy. Enhancing tumor immunogenicity can improve the efficacy of tumor immunotherapy by increasing antigen exposure and presentation, and establishing an inflammatory microenvironment. Here, a multifunctional antigen trapping nanoparticle with indocyanine green (ICG), aluminum hydroxide (Al(OH)) and oxaliplatin (OXA) (PPIAO) has been developed for tumor photoacoustic/ultrasound dual-modality imaging and therapy. The combination of photothermal/photodynamic therapy and chemotherapy induced tumor antigen exposure and release through immunogenic death of tumor cells. A timely capture and storage of antigens by aluminum hydroxide enabled dendritic cells to recognize and present those antigens spatiotemporally. In an ovarian tumor model, the photoacoustic-mediated PPIAO NPs combination therapy achieved a transition from "cold tumor" to "hot tumor" that promoted more CD8 T lymphocytes activation in vivo and intratumoral infiltration, and successfully inhibited the growth of primary and metastatic tumors. An in situ tumor vaccine effect was produced from the treated tumor tissue, assisting mice against the recurrence of tumor cells. This study provided a simple and effective personalized tumor vaccine strategy for better treatment of metastatic and recurrent tumors. The developed multifunctional tumor antigen trapping nanoparticles may be a promising nanoplatform for integrating multimodal imaging monitoring, tumor treatment, and tumor vaccine immunotherapy.
肿瘤的低免疫原性是癌症免疫治疗的主要瓶颈之一。通过增加抗原暴露和呈递以及建立炎症微环境,可以提高肿瘤免疫原性,从而提高肿瘤免疫治疗的疗效。在这里,开发了一种具有吲哚菁绿(ICG)、氢氧化铝(Al(OH)) 和奥沙利铂(OXA)(PPIAO)的多功能抗原捕获纳米颗粒,用于肿瘤光声/超声双模态成像和治疗。光热/光动力治疗和化学治疗的联合作用通过肿瘤细胞免疫原性死亡诱导肿瘤抗原的暴露和释放。氢氧化铝的及时捕获和储存使树突状细胞能够识别和呈递那些抗原,具有时空特异性。在卵巢肿瘤模型中,光声介导的 PPIAO NPs 联合治疗实现了从“冷肿瘤”向“热肿瘤”的转变,促进了体内更多 CD8 T 淋巴细胞的激活和肿瘤内浸润,并成功抑制了原发和转移性肿瘤的生长。从治疗后的肿瘤组织中产生了原位肿瘤疫苗效应,帮助小鼠抵抗肿瘤细胞的复发。这项研究为更好地治疗转移性和复发性肿瘤提供了一种简单有效的个体化肿瘤疫苗策略。开发的多功能肿瘤抗原捕获纳米颗粒可能是一种很有前途的纳米平台,可用于整合多模态成像监测、肿瘤治疗和肿瘤疫苗免疫治疗。