Therapeutic Peptide Strategies Overcome Delivery Hurdles, Integrate AI for Enhanced Precision Medicine

Despite their high specificity, low immunogenicity, and favorable safety profiles, therapeutic peptides (TPs) face significant clinical limitations. Issues such as poor oral bioavailability, rapid enzymatic degradation, and short in vivo half-life severely restrict their utility, preventing them from fully bridging the gap between small molecules and biologics. Current standard-of-care often involves frequent parenteral administration, which impacts patient compliance and treatment efficacy. Addressing these pharmacokinetic challenges is crucial for unlocking the full therapeutic potential of peptides across various disease states.

This comprehensive review systematically analyzed the evolving landscape of therapeutic peptides, focusing on innovative strategies designed to overcome their inherent shortcomings. The authors emphasized key advancements including peptide-drug conjugates (PDCs), peptide-nanoparticle conjugates (PNCs), and stimuli-responsive smart peptide systems. The review also explored multifunctional peptides and peptide-directed delivery of genetic products like CRISPR technology and RNA therapeutics. Furthermore, it highlighted the pivotal role of integrating artificial intelligence (AI)-driven models in peptide design, discovery, tumor diagnostics, and treatment decision-making, providing insights into next-generation peptide-based therapeutics.

The review identified several cutting-edge innovations poised to revolutionize therapeutic peptide applications. Key strategies include peptide-drug conjugates (PDCs) and peptide-nanoparticle conjugates (PNCs), which enhance stability and targeted delivery. Synergistic peptide combinations and stimuli-responsive smart peptide systems were highlighted for their ability to offer controlled release and improved efficacy. Multifunctional peptides demonstrated potential for simultaneous targeting and therapeutic action. The integration of peptides into gene delivery systems, such as those utilizing CRISPR and RNA therapeutics, represents a significant advancement in precision medicine. The review particularly focused on applications in cancer theranostics, immunotherapy, and precision nanomedicine. > The review underscored the transformative impact of artificial intelligence (AI) in accelerating peptide design, optimizing delivery, and enhancing diagnostic precision, marking a pivotal shift in bioinformatic utilization for improved treatment efficiency.