Guanxin Shen, Qianqian Liu, Khurram Shezad, Jun Li, Jun Xie, Yong Xu, Zhiping Zhang, Juan Tao, Chen Shen, Ruijing Liang, Chaohua Yang, Ke Wang, Yi Zhang, Jintao Zhu, Liping Liu, Martin Sullivan
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 HGP10025–33 and TRP2180–188, two melanoma-derived peptides with varied hydrophobicities. The HMSNs with large pore size can improve the encapsulation efficiency of both HGP100 and TRP2 after NH2 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.
HGP100 and TRP2 loaded mesoporous silica nanoparticles are enveloped with monophosphoryl lipid A entrapped lipid bilayers (HMLBs). The vaccine formulations are taken up by dendritic cells to activate both antigen-specific CD8+ and CD4+ T lymphocytes in regional lymph nodes, and inhibit tumor growth and metastasis in prophylactic and metastatic murine melanoma models. The HMLBs provide another opportunity for coencapsulation of adjuvant and multiple peptides with varied hydrophobicities to improve delivery efficiency and enhance antitumor efficacy of conventional vaccinations.