<p>Mannose-Modified Liposome Co-Delivery of Human Papillomavirus Type 16 E7 Peptide and CpG Oligodeoxynucleotide Adjuvant Enhances Antitumor Activity Against Established Large TC-1 Grafted Tumors in Mice</p>

作者：Yan Zhao, Huan Wang, Yang Yang, Wendan Jia, Tong Su, Yuxin Che, Yixin Feng, Xuemei Yuan, Xuelian Wang · 发表于：International Journal of Nanomedicine · 年份：2020 · DOI：10.2147/ijn.s275670 · 被引用次数：42 · 研究领域：Immunotherapy and Immune Responses、RNA Interference and Gene Delivery、Nanoparticle-Based Drug Delivery

Background: Previously, we demonstrated the therapeutic efficacy of a human papillomavirus (HPV) vaccine, including HPV16 E7 peptide and CpG oligodeoxynucleotides (CpG ODN), against small TC-1 grafted tumors. Here, we developed an HPV16 E7 peptide and CpG ODN vaccine delivered using liposomes modified with DC-targeting mannose, Lip E7/CpG, and determined its anti-tumor effects and influence on systemic immune responses and the tumor microenvironment (TME) in a mouse large TC-1 grafted tumor model. Methods: L-alpha-phosphatidyl choline (SPC), cholesterol (CHOL), 1,2-distearoyl- sn -glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol-2000)] (DSPE-PEG-2000), 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) and Mannose-PEG-DSPE, loaded with HPV16 E7 peptide and CpG ODN, were used to construct the Lip E7/CpG vaccine. The anti-tumor effects and potential mechanism of Lip E7/CpG were assessed by assays of tumor growth inhibition, immune cells, in vivo cytotoxic T lymphocyte (CTL) responses and cytokines, chemokines, CD31, Ki67 and p53 expression in the TME. In addition, toxicity of Lip E7/CpG to major organs was evaluated. Results: Lip E7/CpG had a diameter of 122.21± 8.37 nm and remained stable at 4°C for 7 days. Co-delivery of HPV16 E7 peptide and CpG ODN by liposomes exerted potent anti-tumor effects in large (tumor volume ≥ 200mm 3 ) TC-1 grafted tumor-bearing mice with inhibition rates of 80% and 78% relative to the control and Free E7/CpG groups, respec...