Enhanced cancer immunotherapy by microneedle patch-assisted delivery of HBc VLPs based cancer vaccine

Tumor vaccines have made a significant breakthrough in clinical trials of cancer therapy, but have shown limited efficacy. Herein, we develop a novel tumor vaccine delivery strategy through a biodegradable microneedle patch (MN), which allows sustained release of tumor antigen and induces long term anti-tumor response. A tumor antigen peptide (OVA(25)(7-)(264): SIINFEKL) was fused with hepatitis B core (HBc) protein virus like particles (OVA-HBc VLPs) to increase the immunogenicity of tumor antigen. Mesoporous silica nanoparticles (MSN) were adopted as a vaccine adjuvant for enhancing the function of dendritic cells (DCs). OVA-HBc VLPs and MSN were capsulated into microneedles together [MSN/OVA-HBc@MN]. MSN/OVA-HBc@MN could significantly stimulate DC maturation and increase the presentation of OVA on DCs in vitro. MSN/OVA-HBc@MN can effectively stimulate antigen specific anti-tumor immune response and be used as prophylactic vaccines to effectively inhibit tumor formation. Moreover, the addition of CpG-DNA can enhance the therapeutic effect of MSN/OVA-HBc@MN in distant tumors and long term immune memory effect. Our results thus demonstrate that MSN--CpG/OVA-HBc@MN could be as a potential tumor-specific vaccination platform for tumor therapy. (C) 2021 Elsevier Ltd. All rights reserved.