Recent Advances of Cell-Penetrating Peptides and Their Application as Vectors for Delivery of Peptide and Protein-Based Cargo Molecules

Peptides and proteins, two important classes of biomacromolecules, play important roles in the biopharmaceuticals field. As compared with traditional drugs based on small molecules, peptide- and protein-based drugs offer several advantages, although most cannot traverse the cell membrane, a natural...

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Main Authors: Huifeng Zhang, Yanfei Zhang, Chuang Zhang, Huan Yu, Yinghui Ma, Zhengqiang Li, Nianqiu Shi
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/15/8/2093
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author Huifeng Zhang
Yanfei Zhang
Chuang Zhang
Huan Yu
Yinghui Ma
Zhengqiang Li
Nianqiu Shi
author_facet Huifeng Zhang
Yanfei Zhang
Chuang Zhang
Huan Yu
Yinghui Ma
Zhengqiang Li
Nianqiu Shi
author_sort Huifeng Zhang
collection DOAJ
description Peptides and proteins, two important classes of biomacromolecules, play important roles in the biopharmaceuticals field. As compared with traditional drugs based on small molecules, peptide- and protein-based drugs offer several advantages, although most cannot traverse the cell membrane, a natural barrier that prevents biomacromolecules from directly entering cells. However, drug delivery via cell-penetrating peptides (CPPs) is increasingly replacing traditional approaches that mediate biomacromolecular cellular uptake, due to CPPs’ superior safety and efficiency as drug delivery vehicles. In this review, we describe the discovery of CPPs, recent developments in CPP design, and recent advances in CPP applications for enhanced cellular delivery of peptide- and protein-based drugs. First, we discuss the discovery of natural CPPs in snake, bee, and spider venom. Second, we describe several synthetic types of CPPs, such as cyclic CPPs, glycosylated CPPs, and D-form CPPs. Finally, we summarize and discuss cell membrane permeability characteristics and therapeutic applications of different CPPs when used as vehicles to deliver peptides and proteins to cells, as assessed using various preclinical disease models. Ultimately, this review provides an overview of recent advances in CPP development with relevance to applications related to the therapeutic delivery of biomacromolecular drugs to alleviate diverse diseases.
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spelling doaj.art-ab7ecde8d149437d90c0a28c3b3380402023-11-19T02:36:42ZengMDPI AGPharmaceutics1999-49232023-08-01158209310.3390/pharmaceutics15082093Recent Advances of Cell-Penetrating Peptides and Their Application as Vectors for Delivery of Peptide and Protein-Based Cargo MoleculesHuifeng Zhang0Yanfei Zhang1Chuang Zhang2Huan Yu3Yinghui Ma4Zhengqiang Li5Nianqiu Shi6School of Pharmacy, Jilin Medical University, Jilin 132013, ChinaSchool of Pharmacy, Jilin Medical University, Jilin 132013, ChinaSchool of Pharmacy, Jilin Medical University, Jilin 132013, ChinaSchool of Pharmacy, Jilin Medical University, Jilin 132013, ChinaSchool of Pharmacy, Jilin Medical University, Jilin 132013, ChinaKey Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Pharmacy, Jilin Medical University, Jilin 132013, ChinaPeptides and proteins, two important classes of biomacromolecules, play important roles in the biopharmaceuticals field. As compared with traditional drugs based on small molecules, peptide- and protein-based drugs offer several advantages, although most cannot traverse the cell membrane, a natural barrier that prevents biomacromolecules from directly entering cells. However, drug delivery via cell-penetrating peptides (CPPs) is increasingly replacing traditional approaches that mediate biomacromolecular cellular uptake, due to CPPs’ superior safety and efficiency as drug delivery vehicles. In this review, we describe the discovery of CPPs, recent developments in CPP design, and recent advances in CPP applications for enhanced cellular delivery of peptide- and protein-based drugs. First, we discuss the discovery of natural CPPs in snake, bee, and spider venom. Second, we describe several synthetic types of CPPs, such as cyclic CPPs, glycosylated CPPs, and D-form CPPs. Finally, we summarize and discuss cell membrane permeability characteristics and therapeutic applications of different CPPs when used as vehicles to deliver peptides and proteins to cells, as assessed using various preclinical disease models. Ultimately, this review provides an overview of recent advances in CPP development with relevance to applications related to the therapeutic delivery of biomacromolecular drugs to alleviate diverse diseases.https://www.mdpi.com/1999-4923/15/8/2093CPPspeptidesproteinsdiscovery of CPPsnew generation of CPPscargo delivery
spellingShingle Huifeng Zhang
Yanfei Zhang
Chuang Zhang
Huan Yu
Yinghui Ma
Zhengqiang Li
Nianqiu Shi
Recent Advances of Cell-Penetrating Peptides and Their Application as Vectors for Delivery of Peptide and Protein-Based Cargo Molecules
Pharmaceutics
CPPs
peptides
proteins
discovery of CPPs
new generation of CPPs
cargo delivery
title Recent Advances of Cell-Penetrating Peptides and Their Application as Vectors for Delivery of Peptide and Protein-Based Cargo Molecules
title_full Recent Advances of Cell-Penetrating Peptides and Their Application as Vectors for Delivery of Peptide and Protein-Based Cargo Molecules
title_fullStr Recent Advances of Cell-Penetrating Peptides and Their Application as Vectors for Delivery of Peptide and Protein-Based Cargo Molecules
title_full_unstemmed Recent Advances of Cell-Penetrating Peptides and Their Application as Vectors for Delivery of Peptide and Protein-Based Cargo Molecules
title_short Recent Advances of Cell-Penetrating Peptides and Their Application as Vectors for Delivery of Peptide and Protein-Based Cargo Molecules
title_sort recent advances of cell penetrating peptides and their application as vectors for delivery of peptide and protein based cargo molecules
topic CPPs
peptides
proteins
discovery of CPPs
new generation of CPPs
cargo delivery
url https://www.mdpi.com/1999-4923/15/8/2093
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