Cell-Penetrating Peptide-Based Delivery of Macromolecular Drugs: Development, Strategies, and Progress

Cell-penetrating peptides (CPPs), developed for more than 30 years, are still being extensively studied due to their excellent delivery performance. Compared with other vehicles, CPPs hold promise delivering different types of drugs. Here, we review the development process and summarize composition classification CPP-based systems, cellular uptake mechanisms, influencing factors, biological barriers. We also optimization routes macromolecular drug from stability targeting perspectives. Strategies enhanced endosomal escape, which prolong its half-life in blood, improve efficiency stimuli-responsive design comprehensively summarized macromolecule delivery. Finally, after concluding clinical trials extracted necessary conditions a successful system. This provides latest framework drugs summarizes optimized strategies efficiency.