4.7 Review

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

Journal

BIOMEDICINES
Volume 11, Issue 7, Pages -

Publisher

MDPI
DOI: 10.3390/biomedicines11071971

Keywords

cell-penetrating peptide; macromolecular drug delivery; cellular uptake mechanism; biological barrier; optimized strategy

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

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