Preparation of polymeric Janus particles for stimulation of immune cells

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In the proposed work, polymeric nanoparticles will be developed for in vivo antigen-specific stimulation of immune cells for applications in cancer immunotherapy. Specifically, I will prepare two-compartmental poly(lactide-co-glycolide)-based nanoparticles that provide a flexible scaffold for binding tumor-antigens (compartment 1) and release cytokines that are important in shaping the immune response (compartment 2). Polymeric Janus particles will be prepared by electrohydrodynamic (EHD) co-jetting and the two compartments will be modified individually. Compartment 1 will be optimized for antigen-presentation via surface-grafted NHS-ester brushes whereas compartment 2 will be optimized for cytokine release. The grafted polymer brushes will serve as flexible carriers for receptor molecules which trigger antigen-specific activation of immune cells. Grafted brushes combine flexibility of the scaffold and multiple antigen presentation, both crucial for efficient immune cell activation, in an ideal way. Precise control of antigen loading and average distance in compartment 1 will be achieved by controlling the brush properties (grafting density, thickness). Cytokines will be incorporated into compartment 2 and their release will be controlled by adjusting the degradation rate of the polymer via the preparation parameters. By further functionalizing compartment 2 with zwitterionic brushes, prolonged particle retention in the lymph nodes (where immune cells reside) will be achieved.