Innovative Mixed Charge Polymers for Targeted siRNA Delivery in Breast Cancer Treatment (Emerging Themes for Research: Nanomedicine and Bioelectronics Research Center)

The quest for targeted cancer therapies highlights the need for safe and effective siRNA delivery systems to silence key oncogenes. ARID4B, crucial in breast cancer progression, is an ideal candidate for siRNAmediated silencing. However, traditional delivery vectors face inefficiency and toxicity issues. This proposal aims to develop innovative zwitterionic-like polyethylenimine (zPEI) for efficient delivery of siRNA targeting ARID4B, leveraging our findings that zPEI enhances DNA delivery in serum-rich environments. We hypothesize that these modifications will improve siRNA delivery, reduce cytotoxicity, and enhance therapeutic outcomes in breast cancer. Our goal is to establish new RNA delivery platforms for various cancer therapies, starting with ARID4B silencing in breast cancer. We will develop and optimize zPEI polymers to create an advanced siRNA delivery system, identifying optimal formulations through in vitro and in vivo assessments. Supported by our previous findings, we hypothesize that zPEI will provide superior siRNA delivery in the presence of serum and reduced cytotoxicity, enhancing ARID4B-targeting siRNA's therapeutic efficacy in breast cancer.