Biodynamer as a drug potentiator

Novel approaches in treatments and delivery strategies are being highlighted to maximize the effectiveness and overcome the limitations of current medications, such as low solubility, targeting, and stability, as well as developing drug resistance. One such approach is the utilization of sophisticatedly designed functional materials or excipients. In this study, we employ strategies to enhance drug efficacy by developing biocompatible and biofunctional polymers. Biodynamers are protein-based, acid-responsive polymers [1]. These biodynamers utilize dynamic covalent chemistry (DCC) to reversibly polymerize amino acid hydrazides with synthetic amphiphilic monomer (hexaethylene glycol-conjugated carbazole dialdehydes) under acidic conditions. The polymerized biodynamers form single-chain nanorods surrounded by biocompatible ethylene glycol chains through π-π stacking and hydrophobic interactions. Due to the use of DCC, they degrade and undergo local structural changes in disease-specific or intracellular compartment-specific acidic environments. We have confirmed that the dynamicity of these nanorod-shaped polymers enables specific interactions with cell membranes. Firstly, it was confirmed that biodynamers promote endosomal escape approximately 10 times more effectively than commercially available lipid-based carriers through specific interactions within acidic cellular organelles (endosomes) in human cells. Consequently, when using biodynamers for the delivery of mRNA and siRNA, we observed 98% transfection efficiency without compromising cell viability, which is 1.6 times higher than the efficiency of conventional lipid-based carriers [2], [3]. Secondly, we confirmed that biodynamers exhibit specific interactions with Gram-negative bacterial envelopes. Infection sites are acidic, and bacterial cell membranes have the unique characteristic of negatively charged LPS expression. Based on this, we investigated the interactions between the positively charged Arg-based biodynamers and the bacterial cell membrane. As a result, we found that the Arg-biodynamers weaken the bacterial cell membrane, thereby enhancing the activity of co-administered antibiotics by approximately 32 times [4]. Through these studies, we demonstrate that well-designed functional materials can not only function in drug delivery through encapsulation and targeted delivery but also maximize drug efficacy through specific activities in biological environments. This highlights the importance of developing functional polymer materials in the field of drug delivery and is expected to renew interest in this area.