Preparation of polymeric Janus particles for stimulation of immune cells

在拟议的工作中，聚合物纳米颗粒将被开发用于在体内抗原特异性刺激免疫细胞，用于癌症免疫治疗。具体来说，我将准备两室聚（丙交酯-共-乙交酯）为基础的纳米粒子，提供一个灵活的支架结合肿瘤抗原（1室）和释放细胞因子，这是重要的塑造免疫反应（2室）。聚合物Janus颗粒将通过电流体动力学（EHD）共喷射制备，两个隔室将单独改性。Combustion 1将被优化用于通过表面接枝的NHS-酯刷的抗原呈递，而隔室2将被优化用于细胞因子释放。接枝的聚合物刷将作为受体分子的柔性载体，受体分子触发免疫细胞的抗原特异性激活。接枝刷联合收割机结合了支架的灵活性和多种抗原呈递，两者都是以理想的方式有效激活免疫细胞的关键。通过控制刷子特性（移植密度、厚度），可精确控制隔室1中的抗原加载量和平均距离。将细胞因子掺入隔室2中，并通过制备参数调节聚合物的降解速率来控制其释放。通过用两性离子刷进一步功能化隔室2，将实现淋巴结（免疫细胞驻留的地方）中的延长的颗粒保留。

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.