Chalathan Saengruengrit. Synthesis of magnetic nanocomposites for protein delivery. Doctoral Degree(Chemistry). Chulalongkorn University. Office of Academic Resources. : Chulalongkorn University, 2016.
Synthesis of magnetic nanocomposites for protein delivery
Abstract:
In order to develop effective vaccines, an ability to deliver antigen into antigen presenting cells in such a way that the immune responses are induced, must be conquered. This study demonstrates that such requirement can be achieved through the combination of a magnetic field and the relatively non-toxic composite particles of superparamagnetic iron oxide nanoparticles and polymer (SPION-Polymer). In comparison of two biocompatible polymers, poly(lactic-co-glycolic acid) (PLGA) and modified poly(acrylic acid) (mPAA), SPION-PLGA demonstrated stronger magnetic response than SPION-mPAA. We chose SPION-PLGA to load bovine serum albumin (BSA, a protein antigen model). The particles were characterized using various techniques including transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), dynamic light scattering (DLS), infrared spectroscopy (IR) and Superconducting Quantum Interference Device-Vibrating Sample Magnetometer (SQUID-VSM). The SPION-PLGA loading BSA was tested for cytotoxicity and cellular uptake, before delivered them into bone-marrow derived primary dendritic cells (BM-DCs). Significant enhancement of cellular uptake of the 500 nm BSA-loaded SPION-PLGA particles can be achieved under the use of an external magnetic field. Moreover, this combined SPION-PLGA carrier and an external magnetic field can significantly enhance BM-DC maturation by upregulating MHC II, CD80 and CD86 expression. Immune response induction by this strategy is verified through a significant upregulation of the IL-12, IFN-g and IL-6 production. We anticipate these findings to be a starting point for vaccine researches involving the combined magnetic field and SPION-PLGA composite particles.