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

Author:

Sun Zhe1,Huang Jinhai1ORCID,Fishelson Zvi2,Wang Chenhui3,Zhang Sihe3ORCID

Affiliation:

1. School of Life Sciences, Tianjin University, Tianjin 300072, China

2. Department of Cell and Developmental Biology, Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel

3. Department of Cell Biology, School of Medicine, Nankai University, Tianjin 300071, China

Abstract

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.

Funder

National Translational Science Center for Molecular Medicine Fund

Chinese Pharmaceutical Association-Yiling Pharmaceutical Innovation Fund

the Key Research Fund of the Tianjin Project and Team

Key Research and Development Program of Tianjin

the Key Program of the Natural Science Fund of Tianjin

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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