Injectable Hydrogels Coencapsulating Granulocyte-Macrophage Colony-Stimulating Factor and Ovalbumin Nanoparticles to Enhance Antigen Uptake Efficiency

Abstract

The combination of an antigen and adjuvant has synergistic effects on an immune response. Coadministration of an antigen and a granulocyte-macrophage colony-stimulating factor (GM-CSF) hydrogel delivery system will afford a novel strategy for enhancement of an immune response because of the dual role of the hydrogel as a vaccine carrier with a sustained release and a platform for recruiting dendritic cells (DCs). Herein, an injectable poly(caprolactone)-poly(ethylene glycol)-poly(caprolactone) thermosensitive hydrogel coencapsulating GM-CSF and ovalbumin nanoparticles was developed to enhance antigen uptake efficiency. The GM-CSF released from the hydrogel ensured accumulation of DCs; this effect improved the antigen uptake efficiency with the targeted delivery to antigen-presenting cells. Furthermore, the dual delivery system induced a stronger immune effect, including higher CD8 T proportion, interferon γ secretion, and a greater cytotoxic T lymphocyte response, which may benefit from the recruitment of DCs, increasing antigen residence time, and the controllable antigen release owing to the combined effect of the hydrogel and nanoparticles. Meanwhile, the real-time antigen delivery process in vivo was revealed by a noninvasive fluorescence imaging method. All of the results indicated that the visible dual delivery system may have a greater potential for the efficient and trackable vaccine delivery.

Artificial Metalloprotein Nanoanalogues: In Situ Catalytic Production of Oxygen to Enhance Photoimmunotherapeutic Inhibition of Primary and Abscopal Tumor Growth

“…[ 42 ] Among these T cells, the cytotoxic T lymphocytes (CTLs, CD3 + CD4 − CD8 + ) can kill cancer cells, and helper T cells (CD3 + CD4 + CD8 − ) play a vital role in regulating the immune response. [ 43 ] Herein, the distant tumors from mice were harvested on day 8 to detect tumor‐infiltrating CD8 + (CD3 + CD4 − CD8 + ) and CD4 + (CD3 + CD4 + CD8 − ) T cells by flow cytometry. As shown in Figure , the percentages of CD4 + T cells and CD8 + T cells for distant tumors gradually increased from Group 1 to Group 6.…”

Hydrogels for Engineering the Immune System

“…Sun et al designed a vaccine platform comprising a simple physical mixture of thermosensitive poly‐(caprolactone)‐poly (ethylene glycol)‐poly(caprolactone) [PCL‐PEG‐PCL] hydrogels, and chitosan‐modified genipin‐cross‐linked ovalbumin nanoparticles (OVA NPs). [ 109 ] Sustained release of GM‐CSF facilitated recruitment of DCs into hydrogels which significantly increased proportion of CD8+ cells in mouse model ( Figure 4 A). Similarly, Yang et al engineered a similar vaccine formulation by directly trapping DCs and tumor antigens into a self‐assembling nanofiber hydrogel and achieved an enhanced antigen uptake and presentation efficacy (Figure 4B).…”

Nanosystems for Improved Targeted Therapies in Melanoma

“…Sun Z. et al (2018) tried to enhance the antigenic immune response by the co-encapsulation of GM-CSF with ovalbumin nanoparticles in a thermosensitive hydrogel [60]. They proved that the nanoparticle combination achieved superior immune effects [60].…”