Peptide-Enabled Design of Therapeutic Supramolecular Polymers

The physicochemical, biological, and responsive features of supramolecular polymers (SPs) enable their unique applications in many biomedical settings. By leveraging the assembling and biological features of short peptides, we have developed a class of therapeutic supramolecular polymers that are formed by self-assembly of rationally designed peptide-drug conjugates. Depending upon the drug’s intrinsic assembling potential and its water solubility, various peptide designs were adopted to promote the drug’s association into discrete supramolecular polymers that could further entangle into hydrogels. Our results suggest that the critical micellization concentration of an individual SP has a significant impact on their biodistribution and pharmacological behavior for systemic delivery, which is reflected in the maximum tolerated dose, tumor accumulation, toxicity, and eventually the therapeutic efficacy in suppressing tumor growth. On the other hand, the drug-based supramolecular hydrogel can be used for the local delivery and sustainable release of immune-modulating agents, and this localized chemoimmunotherapy hydrogel offers great potential to augment antitumor immune response and to sensitize tumors to immunotherapies in a safe and effective manner.