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Pharmaceutics
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Application Prospects and Challenges of Cell-Penetrating Peptides in Drug Delivery...
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Application Prospects and Challenges of Cell-Penetrating Peptides in Drug Delivery Systems

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Gene and Cell Therapy".

Deadline for manuscript submissions: 30 April 2024 | Viewed by 2165

Special Issue Editor

Dr. Zoltán Bánóczi

E-Mail Website
Guest Editor
Department of Organic Chemistry, Eötvös L. University, 1117 Budapest, Hungary
Interests: cell-penetrating peptide; peptide conjugate; cellular uptake; structure-activity relationship; drug-delivery systems

Special Issue Information

Dear Colleagues,

We are pleased to invite you to submit to the new Special Issue ‘Application Prospects and Challenges of Cell-Penetrating Peptides in Drug Delivery Systems’. Cell-penetrating peptides are a very exciting family of short peptides with diverse structures that can deliver a wide variety of compounds, e.g., small molecules, peptides, proteins, and oligonucleotides, into cells. Despite our growing knowledge, it is still difficult to predict the biological effectiveness of peptides and their conjugates. The huge number of examples in the literature demonstrate the enormous potential of these peptides as a drug delivery system but also highlight the drawbacks that need to be addressed for their successful application; these include non-selective cellular entry, vesicular transport, or rapid clearance.  Although our understanding of the mechanisms of their cellular entry is improving, the pieces of the structure–activity relationships that are most important for the design of peptides are still missing.

This Special Issue aims to emphasize and highlight the applicability of cell-penetrating peptides as drug-delivery agents. Original research papers and reviews regarding newly developed cell-penetrating peptides, cell-penetrating peptide conjugates, the structure–internalization relationship, and the effect of different chemical modifications are welcome.

I look forward to receiving your contributions.

Dr. Zoltán Bánóczi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cell-penetrating peptide
  • peptide conjugate
  • cellular uptake
  • structure-activity relationship
  • drug-delivery systems

Published Papers (2 papers)

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Research

13 pages, 5823 KiB  
Article
Influence of Aza-Glycine Substitution on the Internalization of Penetratin
by Karima Tarchoun, Dóra Soltész, Viktor Farkas, Ho-Jin Lee, Ildikó Szabó and Zoltán Bánóczi
Pharmaceutics 2024, 16(4), 477; https://doi.org/10.3390/pharmaceutics16040477 - 30 Mar 2024
Viewed by 584
Abstract
The cell-penetrating peptide (CPP) penetratin has gained much attention over many years due to its potential role as a transporter for a broad range of cargo into cells. The modification of penetratin has been extensively investigated too. Aza-peptides are peptide analogs in which [...] Read more.
The cell-penetrating peptide (CPP) penetratin has gained much attention over many years due to its potential role as a transporter for a broad range of cargo into cells. The modification of penetratin has been extensively investigated too. Aza-peptides are peptide analogs in which one or more of the amino residues are replaced by a semicarbazide. This substitution results in conformational restrictions and modifications in hydrogen bonding properties, which affect the structure and may lead to enhanced activity and selectivity of the modified peptide. In this work, the Trp residues of penetratin were substituted by aza-glycine or glycine residues to examine the effect of these modifications on the cellular uptake and the internalization mechanism. The substitution of Trp48 or Trp48,56 dramatically reduced the internalization, showing the importance of Trp48 in cellular uptake. Interestingly, while aza-glycine in the position of Trp56 increased the cellular uptake, Gly reduced it. The two Trp-modified derivatives showed altered internalization pathways, too. Based on our knowledge, this is the first study about the effect of aza-amino acid substitution on the cell entry of CPPs. Our results suggest that aza-amino acid insertion is a useful modification to change the internalization of a CPP. Full article
(This article belongs to the Special Issue Application Prospects and Challenges of Cell-Penetrating Peptides in Drug Delivery Systems)
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13 pages, 3069 KiB  
Article
Chemical Modification of Cytochrome C for Acid-Responsive Intracellular Apoptotic Protein Delivery for Cancer Eradication
by Bo Tang, Kwai Man Lau, Yunxin Zhu, Chihao Shao, Wai-Ting Wong, Larry M. C. Chow and Clarence T. T. Wong
Pharmaceutics 2024, 16(1), 71; https://doi.org/10.3390/pharmaceutics16010071 - 04 Jan 2024
Viewed by 1217
Abstract
Delivering bioactive proteins into cells without carriers presents significant challenges in biomedical applications due to limited cell membrane permeability and the need for targeted delivery. Here, we introduce a novel carrier-free method that addresses these challenges by chemically modifying proteins with an acid-responsive [...] Read more.
Delivering bioactive proteins into cells without carriers presents significant challenges in biomedical applications due to limited cell membrane permeability and the need for targeted delivery. Here, we introduce a novel carrier-free method that addresses these challenges by chemically modifying proteins with an acid-responsive cell-penetrating peptide (CPP) for selective intracellular delivery within tumours. Cytochrome C, a protein known for inducing apoptosis, served as a model for intracellular delivery of therapeutic proteins for cancer treatment. The CPP was protected with 2,3-dimethyl maleic anhydride (DMA) and chemically conjugated onto the protein surface, creating an acid-responsive protein delivery system. In the acidic tumour microenvironment, DMA deprotects and exposes the positively charged CPP, enabling membrane penetration. Both in vitro and in vivo assays validated the pH-dependent shielding mechanism, demonstrating the modified cytochrome C could induce apoptosis in cancer cells in a pH-selective manner. These findings provide a promising new approach for carrier-free and tumour-targeted intracellular delivery of therapeutic proteins for a wide range of potential applications. Full article
(This article belongs to the Special Issue Application Prospects and Challenges of Cell-Penetrating Peptides in Drug Delivery Systems)
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