癌症疫苗被认为是通过诱导特异性抗肿瘤免疫反应的有前景的免疫疗法。合理的疫苗接种时间以有效呈现肿瘤相关抗原将增强肿瘤免疫力，是非常需要的。在这里，设计了一种基于聚乳酸-羟基乳酸共聚物（PLGA）的纳米级癌症疫苗，其中包含了工程化肿瘤细胞膜蛋白、mRNA和声敏剂氯铵e6（Ce6），其封装效率很高。这种纳米级疫苗可以在皮下注射后有效地传递到淋巴结的抗原呈递细胞（APCs）中。在APCs中，来自受扰乱剪接类似转移癌细胞的工程化细胞的封装细胞膜和RNA提前提供了转移癌的新抗原。此外，声敏剂Ce6与超声照射促进了mRNA从内体中逃逸，增强了抗原呈递。通过4T1同种小鼠模型，已经证明所提出的纳米疫苗有效地引发抗肿瘤免疫反应，从而预防了癌症转移。©2023 The Authors. Advanced Science由Wiley-VCH GmbH出版。

Cancer vaccine has been considered as a promising immunotherapy by inducing specific anti-tumor immune response. Rational vaccination at suitable time to efficiently present tumor associated antigen will boost tumor immunity and is badly needed. Here, a poly (lactic-co-glycolic acid) (PLGA)-based cancer vaccine of nanoscale is designed, in which engineered tumor cell membrane proteins, mRNAs, and sonosensitizer chlorin e6 (Ce6) are encapsulated at high efficiency. The nanosized vaccine can be efficiently delivered into antigen presentation cells (APCs) in lymph nodes after subcutaneous injection. In the APCs, the encapsulated cell membrane and RNA from engineered cells, which have disturbed splicing resembling the metastatic cells, provide neoantigens of metastatic cancer in advance. Moreover, the sonosensitizer Ce6 together with ultrasound irradiation promotes mRNA escape from endosome, and augments antigen presentation. Through 4T1 syngeneic mouse model, it has been proved that the proposed nanovaccine is efficient to elicit antitumor immunity and thus prevent cancer metastasis.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.