佐剂
免疫系统
抗原
材料科学
生物物理学
化学
生物
免疫学
作者
Jun Xie,Chaohua Yang,Qianqian Liu,Jun Li,Ruijing Liang,Chen Shen,Yi Zhang,Ke Wang,Liping Liu,Khurram Shezad,Martin J. Sullivan,Yong Xu,Guanxin Shen,Juan Tao,Jintao Zhu,Zhiping Zhang
出处
期刊:Small
[Wiley]
日期:2017-09-01
卷期号:13 (40)
被引量:61
标识
DOI:10.1002/smll.201701741
摘要
Abstract Codelivery of combinational antigenic peptides and adjuvant to antigen presenting cells is expected to amplify tumor specific T lymphocytes immune responses while minimizing the possibility of tumor escaping and reducing immune tolerance to single antigenic peptide. However, the varied hydrophobicities of these multivariant derived short antigenic peptides limit their codelivery efficiency in conventional delivery systems. Here, a facile yet effective route is presented to generate monodisperse and stable hollow mesoporous silica nanoparticles (HMSNs) for codelivering of HGP100 25–33 and TRP2 180–188 , two melanoma‐derived peptides with varied hydrophobicities. The HMSNs with large pore size can improve the encapsulation efficiency of both HGP100 and TRP2 after NH 2 modification on the inner hollow core and COOH modification in the porous channels. HGP100 and TRP2 loaded HMSNs (HT@HMSNs) are further enveloped within monophosphoryl lipid A adjuvant entrapped lipid bilayer (HTM@HMLBs), for improved stability/biocompatibility and codelivery efficiency of multiple peptides, adjuvant, and enhanced antitumor immune responses. HTM@HMLBs increase uptake by dendritic cells (DCs) and stimulate DCs maturation efficiently, which further induce the activation of both tumor specific CD8 + and CD4 + T lymphocytes. Moreover, HTM@HMLBs can significantly inhibit tumor growth and lung metastasis in murine melanoma models with good safety profiles. HMSNs enveloped with lipid bilayers (HMLBs) are believed to be a promising platform for codelivery of multiple peptides, adjuvant, and enhancement of antitumor efficacy of conventional vaccinations.
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