(80f) Biomimetic Amphiphilic Polymers for Intracellular Therapeutic Delivery and Theranostic Applications

Biomacromolecules represent a powerful new class of medicine with potential for treatment of a wide variety of previously intractable human diseases. However, it remains a big challenge to effectively deliver them through extracellular and intracellular barriers. There is a need to better understand the mechanisms of entry into the cell cytoplasm and nucleus in order to design optimal delivery systems for biological molecules. On the one hand, this would open up significant opportunities to deliver potent drug payloads against intracellular targets to positively impact human health. In addition this would enable us to develop a more general understanding of the rules governing the uptake of biological molecules into cells. This presentation will cover our recent efforts to design, synthesis and in-vitro/in-vivo evaluation of novel bio-functional polymers. The pH-responsive, metabolite-derived, amphiphilic polymers are designed to mimic factors that enable efficient viral transfection. Strict control over the size, structure, hydrophobicity-hydrophilicity balance and aromaticity of the polymers can effectively manipulate their conformational characteristics and dynamic behaviour in aqueous solution and their interactions with lipid membrane, cell and tissue models. It has been demonstrated that the biomimetic polymers can traverse the extracellular matrix in 3-D multicellular spheroids, reach individual cells in the tumour models, and enable efficient cellular entry and substantial endosomal release of payloads (e.g. siRNA and therapeutic proteins) and imaging moieties into the cytoplasm or the nucleus. This could represent a promising therapeutic delivery platform, suitable for research and theranostic applications in the treatment of various diseases including cancer.