Peptide‐Based Supramolecular Therapeutics for Fighting Major Diseases

Abstract

Peptide‐based supramolecular therapeutics (PST) refer to those theranostic nanomedicines based on peptide or peptide derivatives self‐assembly that are constructed in vitro or in vivo. Benefiting from the inherent advantages of peptides, such as good biocompatibility, high bioactivity, and flexible tunability, the reported PST have shown excellent application prospects in combating many major diseases including cancer, cardiovascular disease, infectious disease, autoimmune disease, metabolic disease, and so on. Through thoughtful design, the PST can be fabricated in various forms, including self‐assembled precursor molecules, functional nano‐assemblies, and macroscopic large‐scale hydrogels. The involved peptides in the PST can play different roles, such as serving drug carriers for effective delivery, acting as scaffold materials for cell culture, and functioning as bioactive sequences for treating diseases. In this review, a comprehensive overview of traditional strategies is provided to build PST and emphasize their therapeutic applications for fighting major diseases that pose a threat to human life and health. Moreover, the main challenges of PST in systems design, therapeutic application, and clinical translation are also briefly discussed. It is hoped that this review can arouse much more attention to be paid for PST and promote its practical application in the biomedical field.

Iterative Design Reveals Molecular Domain Relationships in Supramolecular Peptide–Drug Conjugates

“…sPDCs typically include a small molecule prodrug as a hydrophobic block attached to a more hydrophilic and (typically) β-sheet-forming peptide to yield an amphiphilic molecular design; the prodrug motif promotes hydrophobic association of the resulting amphiphilic molecules in aqueous environments and contributes to the self-assembly of precise nanostructures . The most commonly produced nanoforms are high aspect-ratio one-dimensional nanofibers, which may further engage in physical entanglements to form hydrogels useful as localized drug delivery depots. , The enhanced therapeutic potential of sPDCs has been increasingly appreciated, , and exciting recent advances are sPDC formulations that codeliver both chemotherapies and immunotherapies, , sPDCs that gel in situ on contact with physiological environments, − and the potential to incorporate bioactive targeting and therapeutic functionalities, such as through integrin or collagen binding peptide sequences, , and DNA aptamers . Accordingly, sPDC materials constitute a growing class of peptide-based materials being explored for applications in drug delivery …”

“…8 The most commonly produced nanoforms are high aspect-ratio onedimensional nanofibers, which may further engage in physical entanglements to form hydrogels useful as localized drug delivery depots. 9,10 The enhanced therapeutic potential of sPDCs has been increasingly appreciated, 11,12 and exciting recent advances are sPDC formulations that codeliver both chemotherapies and immunotherapies, 13,14 sPDCs that gel in situ on contact with physiological environments, 13−15 and the potential to incorporate bioactive targeting and therapeutic functionalities, such as through integrin or collagen binding peptide sequences, 9,16 and DNA aptamers. 17 Accordingly, sPDC materials constitute a growing class of peptide-based materials being explored for applications in drug delivery.…”