Development of a polymer-based system for delivery of anti-miR-100 and 125b for the treatment of pancreatic ductal adenocarcinoma

本研究旨在开发一种新型的用于胰腺癌治疗的抗miRNA-100和125b的递送系统。本项目旨在通过基团转移聚合合成具有不同结构和组成、不同比例的DMAEMA和OEGMA的星型和线型共聚聚合物，并利用动态光散射(DLS)、光谱、核磁共振和凝胶渗透色谱等技术表征其物理化学性质。此外，它的目的是优化N/P比率，通过在2D和3D胰腺球体模型中进行细胞活性分析来评估载体的稳定性、安全性和有效性，以及通过研究聚合物处理THP-1来源的巨噬细胞中促炎症细胞因子的表达来评估聚合物在免疫系统中的影响。此外，它还旨在通过流式细胞仪和荧光显微镜来评估合成的聚合物的转染率，并与基准聚合物进行比较。

The research aims to develop a novel delivery system for anti-miRNA-100 and 125b for pancreatic cancer treatment. This project aims to synthesize star and linear co-polymers with different architectures and compositions, varying percentages of DMAEMA and OEGMA, by group transfer polymerization, characterize their physicochemical properties using a range of techniques, including dynamic light scattering (DLS), spectroscopy, NMR and gel permeation chromatography. Furthermore, it aims to optimise N/P ratios and assess the stability, safety profile and efficiency of the carriers by performing cell viability assays in 2D and 3D models of pancreatic spheroids as we as by assessing the effect of the polymers in the immune system by studying the expression of pro-inflammatory cytokines in THP-1 derived macrophages upon treatment with polymers. Moreover, it aims to assess the transfection efficiency of synthesised polymers by flow cytometry and fluorescence microscopy in comparison with benchmark polymers.