Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices , Soochow University , Suzhou , Jiangsu 215123 , China.
ACS Nano. 2018 Jun 26;12(6):5121-5129. doi: 10.1021/acsnano.7b09041. Epub 2018 May 22.
Tumor vaccines for cancer prevention and treatment have attracted tremendous interests in the area of cancer immunotherapy in recent years. In this work, we present a strategy to construct cancer vaccines by encapsulating immune-adjuvant nanoparticles with cancer cell membranes modified by mannose. Poly(d,l-lactide- co-glycolide) nanoparticles are first loaded with toll-like receptor 7 agonist, imiquimod (R837). Those adjuvant nanoparticles (NP-R) are then coated with cancer cell membranes (NP-R@M), whose surface proteins could act as tumor-specific antigens. With further modification with mannose moiety (NP-R@M-M), the obtained nanovaccine shows enhanced uptake by antigen presenting cells such as dendritic cells, which would then be stimulated to the maturation status to trigger antitumor immune responses. With great efficacy to delay tumor development as a prevention vaccine, vaccination with such NP-R@M-M in combination with checkpoint-blockade therapy further demonstrates outstanding therapeutic efficacy to treat established tumors. Therefore, our work presents an innovative way to fabricate cancer nanovaccines, which in principle may be applied for a wide range of tumor types.
近年来,肿瘤疫苗在癌症免疫治疗领域引起了极大的关注。在这项工作中,我们提出了一种通过包裹免疫佐剂纳米粒子并修饰其表面的方法来构建肿瘤疫苗。首先,将肿瘤坏死因子受体 7 激动剂咪喹莫特(R837)负载到聚(丙交酯-共-乙交酯)纳米粒子中。然后,用癌细胞膜(NP-R@M)包裹这些佐剂纳米粒子(NP-R),其表面蛋白可作为肿瘤特异性抗原。进一步用甘露糖修饰(NP-R@M-M)后,得到的纳米疫苗被抗原呈递细胞(如树突状细胞)摄取的能力增强,进而被刺激至成熟状态,从而引发抗肿瘤免疫反应。作为预防疫苗,该纳米疫苗具有显著的抑制肿瘤发展的功效,与检查点阻断治疗联合应用时,对已建立的肿瘤也具有出色的治疗效果。因此,我们的工作提出了一种构建肿瘤纳米疫苗的创新方法,该方法原则上可适用于多种肿瘤类型。
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