Grant: Travel Awards - Institute Community Support

Cancer, a complex disease, often requires advanced treatment strategies. Gene therapy is a promising approach in which we send specific instructions to cells to combat cancer. These instructions can be carried by tiny molecules called siRNA, that has the unique ability to target and disrupt mRNA, thereby inhibiting the production of specific proteins crucial to cancer progression, such as those involved in tumor growth or chemotherapy resistance. A significant challenge in using siRNA is the development of an efficient delivery system for siRNA due to its poor permeability through cell membrane and low stability in biological system. While polyethylene imine (PEI), a polymer, has shown promise in delivering siRNA to cells, the successful complexation and intracellular delivery of siRNA are only achievable with high molecular weight PEI (>20kDa). However, these high molecular weight PEIs are not ideal for clinical applications due to their significant toxicity. On the other hand, low molecular weight PEI, while less toxic, may not effectively transport siRNA to its destination. To address this challenge, our study focuses on the development of a novel siRNA delivery system, by conjugating low molecular weight PEI (2kDa) with a-benzyl carboxylate caprolactone (BCL) at different ratios. This special polymer is designed to act as a reliable carrier, delivering siRNA instructions to the target cells. Our data shows successful preparation of siRNA carriers with suitable characteristics, such as size and charge, based on PEI-BCL. From different structures prepared those at higher BCL to PEI ratios showed lower toxicity and higher activity for the carried siRNA in gene silencing in breast cancer cells. In summary, our study introduces a promising siRNA delivery platform, PEI-BCL, which can significantly enhance the transfection efficacy of siRNA compared to low molecular weight PEI and reduced cytotoxicity compared to conventional siRNA transfecting agents.