Delivery of stromal-derived factor-1α via biocompatible gold nanoparticles promotes dendritic cells viability and migration

Abstract

Combination of cancer immunotherapies and nanotechnology has shown to increase therapeutic efficiency and efficacy with less safety concerns. For an effective vaccine, activation and functional maturation of dendritic cells is a key step for the subsequent adaptive immune responses against cancer. Owing to superior biocompatibility, tunable physicochemical properties, low toxicity in immune cells and ease of functionalization by modifying surface with various biomolecules, gold nanoparticles (AuNP) has been exploded for the development of better dendritic cells (DCs)-based vaccines. AuNPs with biopolymer such as collagen has been revealed to increase biological performance. In the present study, a novel nanocarrier comprising of Au nanoparticles fabricated with collagen biomolecule was used to carry bioactive molecules called stromal-derived factor-1α (SDF-1α), which is known to enhance DCs survival, maturation, and migration, Dynamic light scattering (DLS) analysis showed the particle size of Au-Col-SDF-1α (Au-Col-SDF-1) was 308 ± 3.3 nm. Both UV-Vis absorption and FTIR spectrum analysis demonstrated that SDF-1 successfully conjugated onto Au-Col. Cellular uptake analysis indicated that DCs exhibited an excellent uptake capacity when SDF-1α was carried by Au-Col nanocarrier. In addition, MTT assay and cell cycle analysis revealed that Au-Col-SDF-1 could facilitate viability and proliferation of DCs. Furthermore, Au-Col-SDF-1 could promote DCs migration and upregulate matrix metalloproteinase (MMP) enzymatic activity in DCs as well as enhance the ability of DCs in inducing T cell cytokines production. Moreover, Au-Col-SDF-1 could stimulate DCs to express CXCR4 then secret more SDF-1α to further influence the surrounding DCs. In conclusion, our findings provide a new application by promoting DCs cell viability, migration and ability to enhance T cell cytokine production for a better DC‐based cancer vaccine using a novel AuNP-Col nanocarrier that was bounded with SDF-1α (Au-Col-SDF-1α)