Thermoresponsive nanosponges: Efficient antigen delivery carriers and adjuvants for in vivo vaccination

Abstract

BackgroundVaccination is an effective disease prevention strategy involving immune cell stimulation and formation in response to foreign substances. However, the poor immunogenicity and deliverability of certain antigens necessitate novel methods to establish continuous immunity. Therefore, for efficient antigen delivering and simultaneously performing as a nanoadjuvant, herein, we prepared core (polylactic acid)-shell (poloxamer) thermoresponsive nanosponges (TNSs). MethodsBy simple nanoprecipitation, we prepared the thermoresponsive nanosponges (TNSs) with core-to-shell ratios of 1:2 and 1:20. Thereafter, antigens (ovalbumin, OVA) were loaded into TNSs by swelling behavior. ResultsThe TNSs were prepared with different sizes using differing core-to-shell ratios: TNS1:2 (160 nm) and TNS1:20 (67 nm). When loaded with the model antigen ovalbumin (OVA), TNS1:2 (289 nm) showed a seven-fold higher IL-2 secretion response cross-presentation ability than TNS1:20 (74 nm) and was used in subsequent experiments. TNS1:2 promoted dendritic cell maturation and exhibited high OVA encapsulation (optimal loading: 50 wt%), sufficient long-term stability, and controlled OVA release under physiological conditions. It was not toxic to dendritic cells even at high concentrations. Compared to free OVA, 50 wt% OVA loaded TNS1:2 exhibited better cellular uptake and a superior ability to elicit immune cell IL-2 secretion. The OVA antigen-specific activation of immune cells in mice was examined by monitoring serum IgG levels, cross-presentation to splenocyte CD8+ T-cells, and IFN-γ cytokine levels. ConclusionsThe results highlight TNSs as promising nanoadjuvants and carriers for antigen delivery in vaccine applications.