A Visible Codelivery Nanovaccine of Antigen and Adjuvant with Self-Carrier for Cancer Immunotherapy

Abstract

Codelivery nanovaccines of antigens and adjuvants have achieved positive therapy for cancer immunotherapy. The insufficient immunogenicity of these vaccines leads to the difficulty of eliciting robust immune effects for immune clearance due to the inadequate loading efficiency, complex preparation processes, low safety concerns, and weak immune responses. Herein, a visible codelivery nanovaccine of an antigen and adjuvant based on self-cross-linked antigen nanoparticles (ovalbumin nanoparticles (ONPs)) combined with the adjuvant (CpG) for cancer immunotherapy was prepared using antigens themselves as carriers. ONPs not only provide sufficient antigens for continuous simulation of the immune response with high antigen loading efficiency but also serve as natural carriers of CpG. In vitro and in vivo experiments proved that ONPs-CpG can elicit a robust immune response including DC maturity, T cell activation, and IFN-γ production. ONPs-CpG induced strong tumor-specific immunity and exhibited remarkable antitumor immunotherapy effects in vivo using mouse models of lymphoma. Furthermore, to perform the precise vaccine delivery, the dual fluorescent codelivery nanovaccine was monitored in real time in vivo by the visible imaging method. With regard to migration tracking, fluorescence imaging allowed for both high resolution and sensitivity of visible detection based on the fluorescence of ONPs and CpG. The multifunctional nanovaccine could function as a robust platform for cancer immunotherapy and a visible system for antigen–adjuvant tracking.

Dendritic Cells in Anticancer Vaccination: Rationale for Ex Vivo Loading or In Vivo Targeting

“…Heat shock proteins are one example of SR ligands that can be utilized to achieve DC targeting and activation at the same time [157]. Different nanosubstance-based approaches might be also helpful, since several nanosubstances utilized to deliver tumor antigens to a specific DC receptor, such as glycodendrimers and nanoemulsions, have been shown to be self-adjuvant [90,131,190].…”

Better Adjuvants for Better Vaccines: Progress in Adjuvant Delivery Systems, Modifications, and Adjuvant–Antigen Codelivery

“…However, this bionic design will make the vaccine components appear complex and difficult to control. Another trend is to simplify the vaccines; for example, the antigen itself can be used as a delivery carrier, with the adjuvant inserted on the surface of the antigen by coupling to form an extremely simplified antigen-adjuvant complex [134][135][136]. However, this method may result in missing or blocking of some epitopes during the modification process.…”

Advancements in prophylactic and therapeutic nanovaccines

“…Calcium nanoparticles have also been reported for their superior adjuvant property with DNA vaccines and to confer mucosal immunity. They can also induce enhanced antibody production against viral antigens as compared to aluminum adjuvants [121] .…”