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Cells
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Cell-Penetrating Peptides (CPPs) in Cancer: From Molecular Mechanisms to Applications...
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Cell-Penetrating Peptides (CPPs) in Cancer: From Molecular Mechanisms to Applications in Diagnostic and Therapeutic Opportunities

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 14002

Special Issue Editors

Dr. Tohru Yamada

E-Mail Website
Guest Editor
Department of Surgery, Division of Surgical Oncology, University of Illinois, Chicago, IL, USA
Interests: brain tumors; molecular biology; protein/peptide chemistry; cell biology; basic and translational cancer biology
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Pu Chen

E-Mail Website
Guest Editor
Department of Chemical Engineering, Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, ON, Canada
Interests: the interface of materials, biomedicine and energy, with applications in drug and gene delivery, protein-lipid interactions, emulsification, coating, energy storage and conversion
Dr. Lei Zhang

E-Mail Website
Guest Editor
Department of Chemical Engineering, Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, ON, Canada
Interests: peptide design and biointerfaces; peptides for drug delivery; microfluidic device development; nano-functional materials; food science and biomedicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cell-penetrating peptides (CPPs), also known as protein transduction domains (PTDs), are generally short peptides that have been widely studied. Since the first CPP was discovered ~30 years ago, several novel mechanisms and applications of CPPs have been reported.

Given that synthetic and natural CPPs can deliver several types of bioactive cargo, including proteins, peptides, DNA/RNA and chemotherapeutic and imaging agents, into cells, CPPs have been used in preclinical and clinical research. It is evident that CPPs have gained significant attention over the last decade, and they have great potential to develop the next-generation approaches to fight against cancer.

As such, we welcome original research articles, reviews, and perspectives focusing on recent advances in cancer research with CPPs. Manuscripts describing solely bioinformatics or in silico computational analysis that are not accompanied by biological validation are out-of-scope for this topic. We are looking for contributions that primarily focus on CPPs for various types of cancer, including rare diseases.

Dr. Tohru Yamada
Prof. Dr. Pu Chen
Dr. Lei Zhang
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. Cells is an international peer-reviewed open access semimonthly 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 2700 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

  • tumors
  • cellular internalization
  • targeting delivery
  • cargo molecule conjugations
  • tumor imaging
  • toxicity

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Published Papers (4 papers)

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Research

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20 pages, 3667 KiB  
Article
DPEP Inhibits Cancer Cell Glucose Uptake, Glycolysis and Survival by Upregulating Tumor Suppressor TXNIP
by Qing Zhou, Trang Thi Thu Nguyen, Jeong-Yeon Mun, Markus D. Siegelin and Lloyd A. Greene
Cells 2024, 13(12), 1025; https://doi.org/10.3390/cells13121025 - 12 Jun 2024
Cited by 1 | Viewed by 1692
Abstract
We have designed cell-penetrating peptides that target the leucine zipper transcription factors ATF5, CEBPB and CEBPD and that promote apoptotic death of a wide range of cancer cell types, but not normal cells, in vitro and in vivo. Though such peptides have the [...] Read more.
We have designed cell-penetrating peptides that target the leucine zipper transcription factors ATF5, CEBPB and CEBPD and that promote apoptotic death of a wide range of cancer cell types, but not normal cells, in vitro and in vivo. Though such peptides have the potential for clinical application, their mechanisms of action are not fully understood. Here, we show that one such peptide, Dpep, compromises glucose uptake and glycolysis in a cell context-dependent manner (in about two-thirds of cancer lines assessed). These actions are dependent on induction of tumor suppressor TXNIP (thioredoxin-interacting protein) mRNA and protein. Knockdown studies show that TXNIP significantly contributes to apoptotic death in those cancer cells in which it is induced by Dpep. The metabolic actions of Dpep on glycolysis led us to explore combinations of Dpep with clinically approved drugs metformin and atovaquone that inhibit oxidative phosphorylation and that are in trials for cancer treatment. Dpep showed additive to synergistic activities in all lines tested. In summary, we find that Dpep induces TXNIP in a cell context-dependent manner that in turn suppresses glucose uptake and glycolysis and contributes to apoptotic death of a range of cancer cells. Full article
(This article belongs to the Special Issue Cell-Penetrating Peptides (CPPs) in Cancer: From Molecular Mechanisms to Applications in Diagnostic and Therapeutic Opportunities)
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15 pages, 3479 KiB  
Article
Functional Peptides from SARS-CoV-2 Binding with Cell Membrane: From Molecular Dynamics Simulations to Cell Demonstration
by Yun Hao, Rongrong Wu, Fenghua Wang, Liwei Zhang, Zengkai Wang, Xiaolu Song and Lei Liu
Cells 2022, 11(11), 1738; https://doi.org/10.3390/cells11111738 - 25 May 2022
Cited by 1 | Viewed by 2177
Abstract
Herein, we have verified the interaction between the functional peptides from the SARS-CoV-2 and cell membrane, and we further proved that peptides exhibit little membrane disruption. The specific amino acids (Lys, Ile, Glu, Asn, Gln, etc.) with charge or hydrophobic residues play a [...] Read more.
Herein, we have verified the interaction between the functional peptides from the SARS-CoV-2 and cell membrane, and we further proved that peptides exhibit little membrane disruption. The specific amino acids (Lys, Ile, Glu, Asn, Gln, etc.) with charge or hydrophobic residues play a significant role during the functional-peptide binding to membrane. The findings could provide the hints related to viral infection and also might pave the way for development of new materials based on peptides with membrane-binding activity, which would enable functional peptides further as peptide adjuvants, in order to help deliver the cancer drug into tumor cells for the efficient tumor therapy. Full article
(This article belongs to the Special Issue Cell-Penetrating Peptides (CPPs) in Cancer: From Molecular Mechanisms to Applications in Diagnostic and Therapeutic Opportunities)
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Review

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18 pages, 989 KiB  
Review
Ocular Delivery of Therapeutic Agents by Cell-Penetrating Peptides
by Nguyễn Thị Thanh Nhàn, Daniel E. Maidana and Kaori H. Yamada
Cells 2023, 12(7), 1071; https://doi.org/10.3390/cells12071071 - 1 Apr 2023
Cited by 13 | Viewed by 5046
Abstract
Cell-penetrating peptides (CPPs) are short peptides with the ability to translocate through the cell membrane to facilitate their cellular uptake. CPPs can be used as drug-delivery systems for molecules that are difficult to uptake. Ocular drug delivery is challenging due to the structural [...] Read more.
Cell-penetrating peptides (CPPs) are short peptides with the ability to translocate through the cell membrane to facilitate their cellular uptake. CPPs can be used as drug-delivery systems for molecules that are difficult to uptake. Ocular drug delivery is challenging due to the structural and physiological complexity of the eye. CPPs may be tailored to overcome this challenge, facilitating cellular uptake and delivery to the targeted area. Retinal diseases occur at the posterior pole of the eye; thus, intravitreal injections are needed to deliver drugs at an effective concentration in situ. However, frequent injections have risks of causing vision-threatening complications. Recent investigations have focused on developing long-acting drugs and drug delivery systems to reduce the frequency of injections. In fact, conjugation with CPP could deliver FDA-approved drugs to the back of the eye, as seen by topical application in animal models. This review summarizes recent advances in CPPs, protein/peptide-based drugs for eye diseases, and the use of CPPs for drug delivery based on systematic searches in PubMed and clinical trials. We highlight targeted therapies and explore the potential of CPPs and peptide-based drugs for eye diseases. Full article
(This article belongs to the Special Issue Cell-Penetrating Peptides (CPPs) in Cancer: From Molecular Mechanisms to Applications in Diagnostic and Therapeutic Opportunities)
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31 pages, 4374 KiB  
Review
Recent Advances of Studies on Cell-Penetrating Peptides Based on Molecular Dynamics Simulations
by Jun Ouyang, Yuebiao Sheng and Wei Wang
Cells 2022, 11(24), 4016; https://doi.org/10.3390/cells11244016 - 12 Dec 2022
Cited by 11 | Viewed by 4032
Abstract
With the ability to transport cargo molecules across cell membranes with low toxicity, cell-penetrating peptides (CPPs) have become promising candidates for next generation peptide-based drug delivery vectors. Over the past three decades since the first CPP was discovered, a great deal of work [...] Read more.
With the ability to transport cargo molecules across cell membranes with low toxicity, cell-penetrating peptides (CPPs) have become promising candidates for next generation peptide-based drug delivery vectors. Over the past three decades since the first CPP was discovered, a great deal of work has been done on the cellular uptake mechanisms and the applications for the delivery of therapeutic molecules, and significant advances have been made. But so far, we still do not have a precise and unified understanding of the structure–activity relationship of the CPPs. Molecular dynamics (MD) simulations provide a method to reveal peptide–membrane interactions at the atomistic level and have become an effective complement to experiments. In this paper, we review the progress of the MD simulations on CPP–membrane interactions, including the computational methods and technical improvements in the MD simulations, the research achievements in the CPP internalization mechanism, CPP decoration and coupling, and the peptide-induced membrane reactions during the penetration process, as well as the comparison of simulated and experimental results. Full article
(This article belongs to the Special Issue Cell-Penetrating Peptides (CPPs) in Cancer: From Molecular Mechanisms to Applications in Diagnostic and Therapeutic Opportunities)
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