Integrins and Tumor Microenvironment, New Perspectives in Targeted Treatments

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 2984

Special Issue Editors


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Guest Editor
Experimental Pathology and Oncology Section of the Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale GB Morgagni 50, 50134 Firenze, Italy
Interests: tumor microenvironment (TME); cancer cell biology; extracellular acidity; nanomedicine; targeted drug delivery and personalized anticancer therapy
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Co-Guest Editor
Department of Chemistry “Ugo Schiff”, University of Florence, 50019 Sesto Fiorentino, Italy
Interests: drug discovery; organic synthesis; medicinal chemistry; molecular imaging; diversity-oriented synthesis; peptidomimetics; chemoinformatics; enzyme inhibitors; angiogenesis; Alzheimer’s disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Integrins are a family of cell surface receptors with a longstanding history in cancer. The integrin-mediated binding of extracellular matrix components (ECM) by cancer cells leads to essential signaling for cancer cell survival, proliferation, migration, extravasation, and metastatic dissemination to secondary organs.

Recently, the role of integrins in cancer has been enriched with further peculiarities, mostly because of the emerging role of the tumor microenvironment (TME) in the promotion of cancer aggressiveness and resistance to therapy. Indeed, integrins are expressed not only on cancer cells, but also on stromal cells, such as endothelial cells and cancer-associated fibroblasts (CAFs), and on host immune cells, such as tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs).

Thus, the aim of this issue is to unravel the role of integrins in cancer–TME crosstalk, exploring novel molecular pathways by which integrins might promote cancer progression and resistance to anticancer therapy, and suggesting innovative targets for therapeutic interventions. Translational approaches and contributions arising from different disciplines such as molecular oncology, pharmacology, and organic chemistry will be welcome to develop innovative and personalized anticancer treatment.

We solicit contributions on all topics connected to this area, including, but not limited to:

  • Integrins in cancer cell – TME interactions driving drug resistance
  • Integrins in cancer immune evasion strategies
  • Development of antibody/small-molecule–drug conjugates
  • Integrins as tools for molecular imaging

Dr. Francesca Bianchini
Dr. Andrea Trabocchi
Guest Editors

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. Cancers 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 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

  • integrins
  • cancer
  • tumor microenvironment
  • stromal cells
  • immune cells
  • drug development

Published Papers (1 paper)

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Research

17 pages, 10079 KiB  
Article
cRGD-Functionalized Silk Fibroin Nanoparticles: A Strategy for Cancer Treatment with a Potent Unselective Naphthalene Diimide Derivative
by Valentina Pirota, Giovanni Bisbano, Massimo Serra, Maria Luisa Torre, Filippo Doria, Elia Bari and Mayra Paolillo
Cancers 2023, 15(6), 1725; https://doi.org/10.3390/cancers15061725 - 11 Mar 2023
Cited by 7 | Viewed by 2176
Abstract
Developing drug delivery systems to target cytotoxic drugs directly into tumor cells is still a compelling need with regard to reducing side effects and improving the efficacy of cancer chemotherapy. In this work, silk fibroin nanoparticles (SFNs) have been designed to load a [...] Read more.
Developing drug delivery systems to target cytotoxic drugs directly into tumor cells is still a compelling need with regard to reducing side effects and improving the efficacy of cancer chemotherapy. In this work, silk fibroin nanoparticles (SFNs) have been designed to load a previously described cytotoxic compound (NDI-1) that disrupts the cell cycle by specifically interacting with non-canonical secondary structures of DNA. SFNs were then functionalized on their surface with cyclic pentapeptides incorporating the Arg-Gly-Asp sequence (cRGDs) to provide active targeting toward glioma cell lines that abundantly express ανβ3 and ανβ5 integrin receptors. Cytotoxicity and selective targeting were assessed by in vitro tests on human glioma cell lines U373 (highly-expressing integrin subunits) and D384 cell lines (low-expressing integrin subunits in comparison to U373). SFNs were of nanometric size (d50 less than 100 nm), round shaped with a smooth surface, and with a negative surface charge; overall, these characteristics made them very likely to be taken up by cells. The active NDI-1 was loaded into SFNs with high encapsulation efficiency and was not released before the internalization and degradation by cells. Functionalization with cRGDs provided selectivity in cell uptake and thus cytotoxicity, with a significantly higher cytotoxic effect of NDI-1 delivered by cRGD-SFNs on U373 cells than on D384 cells. This manuscript provides an in vitro proof-of-concept of cRGD-silk fibroin nanoparticles’ active site-specific targeting of tumors, paving the way for further in vivo efficacy tests. Full article
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