Rongjun Chen
Imperial College London, UK
Title: Bio-inspired anionic polymers as a platform for designing novel nanoscale intracellular drug delivery systems
Biography
Biography: Rongjun Chen
Abstract
It remains a major challenge to effectively deliver therapeutic agents, in particular macromolecules, through negatively charged lipid membrane barriers. It is the most limiting step preventing successful implementation of macromolecule-based cell modification and intracellular therapies. This is due to endosomal entrapment of macromolecules and their degradation in lysosomes. Many researchers have used cationic delivery systems to address this challenge. However, the positive charge could cause some issues, such as unfavorable biodistribution, rapid renal clearance and high non-specific cytotoxicity. This presentation presents an alternative delivery strategy based on an anionic drug delivery platform. It covers our recent efforts on design and synthesis of novel anionic, viral-peptide-mimicking, pH-responsive, metabolite-derived polymers, and evaluation of their use in intracellular drug delivery in vitro and in vivo. Strict control over the size, structure, hydrophobicity-hydrophilicity balance and sequence of the polymers can effectively manipulate interactions with lipid membrane, cell and tissue models. It has been demonstrated that the biomimetic polymers can successfully traverse the extracellular matrix in three-dimensional multicellular spheroids, and also enable efficient loading of a wide range of macromolecules into the cell interior. This can represent a versatile delivery platform, suitable for targeted therapeutic delivery and cell therapy for treatment of various diseases including but not limited to cancer.