(78a) Drugs As Biomaterials Building Blocks and Immune Boosters

Leveraging the self-assembly potential of therapeutic agents presents an exciting avenue to create novel supramolecular biomaterials with enhanced drug functionality and efficacy. This presentation will explore our recent progress in in using drugs of natural origin as molecular building units to engineer therapeutic supramolecular polymers (SPs). By examining the influence of molecular design, assembly conditions, and kinetic pathways, we have developed a series of SPs that exhibit unique physicochemical and biological properties which enable their unique and important biomedical applications. Depending upon the drug’s intrinsic assembling potential and its water solubility, various peptide-drug conjugate designs were adopted to promote the drug’s association into discrete supramolecular polymers that could further entangle into hydrogels under physiological conditions. Our findings indicate that the critical micellization concentration of an individual SP significantly influences its biodistribution and pharmacological behavior for systemic delivery, impacting the maximum tolerated dose, tumor accumulation, toxicity, and ultimately, the therapeutic efficacy in suppressing tumor growth. In addition, drug-based supramolecular hydrogels have been employed for the local delivery and sustained release of immune-modulating agents. This localized chemoimmunotherapy hydrogel demonstrates considerable potential to enhance antitumor immune responses and sensitize tumors to immunotherapies in a safer and more effective manner.