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Research on Peptide-Drug Conjugates and Their Targets in Cancer Therapies
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Research on Peptide-Drug Conjugates and Their Targets in Cancer Therapies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 4278

Special Issue Editor

Prof. Dr. Nuno Vale

E-Mail Website
Guest Editor
Faculty of Medicine, University of Porto, Porto, Portugal
Interests: cancer Therapy; drug repurposing; peptides in medicine; in silico pharmacology; precision medicine

Special Issue Information

Dear Colleagues,

New advances in precision medicine for the field of oncology may have a special ally: peptides. Peptides’ unique features of block construction allow the right choice of position for certain amino acids and eventual structural change. In addition, peptide–drug conjugates have been gaining interest and are now clinically established for cancer therapy. In 2018,  the first peptide–drug conjugate used in a therapeutic setting was approved by the FDA. Peptides with intelligent linkers or therapeutic cargos improve efficacy and tumor selectivity. Therefore, the approach of peptide-based and receptor-mediated drug delivery improves the treatment efficacy of medicinal compounds. This Special Issue, titled “Peptide–Drug Conjugates and Their Targets in Cancer Therapies”, will focus on fundamental research on peptide–drug conjugates and their role in cancer therapies. Experimental papers sharing new data and up-to-date review articles are welcome.

Prof. Dr. Nuno Vale
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • cancer therapies
  • peptide-drug conjugates
  • tumor selectivity
  • precision medicine

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Published Papers (2 papers)

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Research

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27 pages, 8864 KiB  
Article
Prediction of Drug Synergism between Peptides and Antineoplastic Drugs Paclitaxel, 5-Fluorouracil, and Doxorubicin Using In Silico Approaches
by Nuno Vale, Mariana Pereira, Joana Santos, Catarina Moura, Lara Marques and Diana Duarte
Int. J. Mol. Sci. 2023, 24(1), 69; https://doi.org/10.3390/ijms24010069 - 21 Dec 2022
Cited by 6 | Viewed by 1683
Abstract
Chemotherapy is the main treatment for most early-stage cancers; nevertheless, its efficacy is usually limited by drug resistance, toxicity, and tumor heterogeneity. Cell-penetrating peptides (CPPs) are small peptide sequences that can be used to increase the delivery rate of chemotherapeutic drugs to the [...] Read more.
Chemotherapy is the main treatment for most early-stage cancers; nevertheless, its efficacy is usually limited by drug resistance, toxicity, and tumor heterogeneity. Cell-penetrating peptides (CPPs) are small peptide sequences that can be used to increase the delivery rate of chemotherapeutic drugs to the tumor site, therefore contributing to overcoming these problems and enhancing the efficacy of chemotherapy. The drug combination is another promising strategy to overcome the aforementioned problems since the combined drugs can synergize through interconnected biological processes and target different pathways simultaneously. Here, we hypothesized that different peptides (P1–P4) could be used to enhance the delivery of chemotherapeutic agents into three different cancer cells (HT-29, MCF-7, and PC-3). In silico studies were performed to simulate the pharmacokinetic (PK) parameters of each peptide and antineoplastic agent to help predict synergistic interactions in vitro. These simulations predicted peptides P2–P4 to have higher bioavailability and lower Tmax, as well as the chemotherapeutic agent 5-fluorouracil (5-FU) to have enhanced permeability properties over other antineoplastic agents, with P3 having prominent accumulation in the colon. In vitro studies were then performed to evaluate the combination of each peptide with the chemotherapeutic agents as well as to assess the nature of drug interactions through the quantification of the Combination Index (CI). Our findings in MCF-7 and PC-3 cancer cells demonstrated that the combination of these peptides with paclitaxel (PTX) and doxorubicin (DOXO), respectively, is not advantageous over a single treatment with the chemotherapeutic agent. In the case of HT-29 colorectal cancer cells, the combination of P2–P4 with 5-FU resulted in synergistic cytotoxic effects, as predicted by the in silico simulations. Taken together, these findings demonstrate that these CPP6-conjugates can be used as adjuvant agents to increase the delivery of 5-FU into HT-29 colorectal cancer cells. Moreover, these results support the use of in silico approaches for the prediction of the interaction between drugs in combination therapy for cancer. Full article
(This article belongs to the Special Issue Research on Peptide-Drug Conjugates and Their Targets in Cancer Therapies)
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Review

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13 pages, 4651 KiB  
Review
A Second Life for MAP, a Model Amphipathic Peptide
by Sara Silva, Kaido Kurrikoff, Ülo Langel, António J. Almeida and Nuno Vale
Int. J. Mol. Sci. 2022, 23(15), 8322; https://doi.org/10.3390/ijms23158322 - 28 Jul 2022
Cited by 6 | Viewed by 2111
Abstract
Cell-penetrating peptides (CPP) have been shown to be efficient in the transport of cargoes into the cells, namely siRNA and DNA, proteins and peptides, and in some cases, small therapeutics. These peptides have emerged as a solution to increase drug concentrations in different [...] Read more.
Cell-penetrating peptides (CPP) have been shown to be efficient in the transport of cargoes into the cells, namely siRNA and DNA, proteins and peptides, and in some cases, small therapeutics. These peptides have emerged as a solution to increase drug concentrations in different tissues and various cell types, therefore having a relevant therapeutic relevance which led to clinical trials. One of them, MAP, is a model amphipathic peptide with an α-helical conformation and both hydrophilic and hydrophobic residues in opposite sides of the helix. It is composed of a mixture of alanines, leucines, and lysines (KLALKLALKALKAALKLA). The CPP MAP has the ability to translocate oligonucleotides, peptides and small proteins. However, taking advantage of its unique properties, in recent years innovative concepts were developed, such as in silico studies of modelling with receptors, coupling and repurposing drugs in the central nervous system and oncology, or involving the construction of dual-drug delivery systems using nanoparticles. In addition to designs of MAP-linked vehicles and strategies to achieve highly effective yet less toxic chemotherapy, this review will be focused on unique molecular structure and how it determines its cellular activity, and also intends to address the most recent and frankly motivating issues for the future. Full article
(This article belongs to the Special Issue Research on Peptide-Drug Conjugates and Their Targets in Cancer Therapies)
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