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: 30 April 2024 | Viewed by 9265

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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
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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
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

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Keywords

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

Published Papers (3 papers)

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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
Viewed by 1733
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
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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 - 01 Apr 2023
Cited by 8 | Viewed by 3914
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
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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 9 | Viewed by 2766
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
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