Ultrasound Responsive Nanovaccine Armed with Engineered Cancer Cell Membrane and RNA to Prevent Foreseeable Metastasis

超声响应纳米疫苗配备工程癌细胞膜和 RNA 以防止可预见的转移

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作者:Wenqi Sun, Panpan Ji, Tian Zhou, Zhelong Li, Changyang Xing, Liang Zhang, Mengying Wei, Guodong Yang, Lijun Yuan

Abstract

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.

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