Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

New Advances on Photosensitiser or Inhibitors Molecules for Cancer Treatment

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

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 (15 March 2024) | Viewed by 6377

Share This Special Issue

Special Issue Editor

Dr. Maria Raposo

E-Mail Website
Guest Editor

Laboratory for Instrumentation, Biomedical Engineering and Radiation Physics (LIBPhys-NOVA), Department of Physics, NOVA School of Science and Technology, NOVA University of Lisbon, Campus FCT-NOVA, 2829-516 Caparica, Portugal
Interests: disease diagnosis; biosensors; biomarker; human health monitoring
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The photodynamic therapy concept in which low energy radiation is used on cancer cells with added DNA targeted photosensitizing molecules. The irradiation reaching these molecules enhances the generation of reactive oxygen species (ROS) which possesses cytotoxic effect on DNA. The use of photosensitizing molecules, which can intercalate with DNA helix through physical interactions instead of covalent bonds, prevents damage to normal cells and create radicals in cancer cells when submitted to radiation. But the action of photosensitizing molecules can be maximized if the DNA repair machinery is constrained by affecting the DNA repair proteins using inhibitor molecules that can reduce the effect of the repair and thus sensitize the cells for radiation therapy. This Special Issue of IJMS focuses on the latest developments on new photosensitiser or inhibitors molecules and on the effect of photosensitiser or inhibitors molecules encapsulated or not on biological molecules as DNA and/or DNA repair proteins and on cells in presence of radiation. This Special Issue, “New Advances on Photosensitiser or Inhibitors Molecules for Cancer Treatment”, invites review articles and full-length papers that explore the development or/and the role of photosensitiser or inhibitors molecules near of biological molecules or of cells in presence of radiation. Moreover, papers providing new insights into the development of new systems of encapsulation of these photosensitiser or inhibitors molecules for easier delivery to tumour area are also encouraged.

Dr. Maria Raposo
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

photosensitiser molecules
inhibitors molecules
biomolecules damage
DNA-intercalators
oxidative stress
cell/tissue specificity
drug delivery systems
photodynamic therapy

Published Papers (5 papers)

Download All Papers

Research

17 pages, 3275 KiB

Open AccessArticle

Hijacking 5-Fluorouracil Chemoresistance in Triple Negative Breast Cancer via microRNAs-Loaded Chitosan Nanoparticles

by Sherif Ashraf Fahmy, Noha Khalil Mahdy, Adham H. Mohamed, Fatma A. Mokhtar and Rana A. Youness

Int. J. Mol. Sci. 2024, 25(4), 2070; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25042070 - 08 Feb 2024

Viewed by 948

Abstract

Chemotherapy is still the mainstay of treatment for triple-negative breast cancer (TNBC) patients. Yet only 20% of TNBC patients show a pathologic complete response (pCR) after neoadjuvant chemotherapy. 5-Fluorouracil (5-FU) is a stable cornerstone in all recommended chemotherapeutic protocols for TNBC patients. However, TNBC patients’ innate or acquired chemoresistance rate for 5-FU is steeply escalating. This study aims to unravel the mechanism behind the chemoresistance of 5-FU in the aggressive TNBC cell line, MDA-MB-231 cells, to explore further the role of the tumor suppressor microRNAs (miRNAs), miR-1275, miR-615-5p, and Let-7i, in relieving the 5-FU chemoresistance in TNBC, and to finally provide a translational therapeutic approach to co-deliver 5-FU and the respective miRNA oligonucleotides using chitosan-based nanoparticles (CsNPs). In this regard, cellular viability and proliferation were investigated using MTT and BrdU assays, respectively. 5-FU was found to induce JAK/STAT and PI3K/Akt/mTOR pathways in MDA-MB-231 cells with contaminant repression of their upstream regulators miR-1275, miR-615-5p, and Let-7i. Moreover, CsNPs prepared using the ionic gelation method were chosen and studied as nanovectors of 5-FU and a combination of miRNA oligonucleotides targeting TNBC. The average particle sizes, surface charges, and morphologies of the different CsNPs were characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. In addition, the encapsulation efficiency (EE%), drug loading capacity (DLC%), and release manner at two different pH values were assessed. In conclusion, the novel CsNPs co-loaded with 5-FU and the combination of the three miRNA oligonucleotides demonstrated synergistic activity and remarkable repression in cellular viability and proliferation of TNBC cells through alleviating the chemoresistance to 5-FU. Full article

(This article belongs to the Special Issue New Advances on Photosensitiser or Inhibitors Molecules for Cancer Treatment)

► Show Figures

Figure 1

14 pages, 9741 KiB

Open AccessArticle

HSA-ZW800-PEG for Enhanced Optophysical Stability and Tumor Targeting

by Paul Jang, Jinhui Ser, Kevin Cardenas, Hajin Joanne Kim, Morgan Hickey, Jiseon Jang, Jason Gladstone, Aisha Bailey, Jason Dinh, Vy Nguyen, Emma DeMarco, Surbhi Srinivas, Homan Kang, Satoshi Kashiwagi, Kai Bao, Atsushi Yamashita and Hak Soo Choi

Int. J. Mol. Sci. 2024, 25(1), 559; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25010559 - 31 Dec 2023

Cited by 1 | Viewed by 878

Abstract

Small molecule fluorophores often face challenges such as short blood half-life, limited physicochemical and optical stability, and poor pharmacokinetics. To overcome these limitations, we conjugated the zwitterionic near-infrared fluorophore ZW800-PEG to human serum albumin (HSA), creating HSA-ZW800-PEG. This conjugation notably improves chemical, physical, and optical stability under physiological conditions, addressing issues commonly encountered with small molecules in biological applications. Additionally, the high molecular weight and extinction coefficient of HSA-ZW800-PEG enhances biodistribution and tumor targeting through the enhanced permeability and retention effect. The unique distribution and elimination dynamics, along with the significantly extended blood half-life of HSA-ZW800-PEG, contribute to improved tumor targetability in both subcutaneous and orthotopic xenograft tumor-bearing animal models. This modification not only influences the pharmacokinetic profile, affecting retention time and clearance patterns, but also enhances bioavailability for targeting tissues. Our study guides further development and optimization of targeted imaging agents and drug-delivery systems. Full article

(This article belongs to the Special Issue New Advances on Photosensitiser or Inhibitors Molecules for Cancer Treatment)

► Show Figures

Figure 1

36 pages, 9847 KiB

Open AccessArticle

Imidazo-Pyrazole-Loaded Palmitic Acid and Polystyrene-Based Nanoparticles: Synthesis, Characterization and Antiproliferative Activity on Chemo-Resistant Human Neuroblastoma Cells

by Giulia Elda Valenti, Barbara Marengo, Marco Milanese, Guendalina Zuccari, Chiara Brullo, Cinzia Domenicotti and Silvana Alfei

Int. J. Mol. Sci. 2023, 24(19), 15027; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241915027 - 09 Oct 2023

Cited by 1 | Viewed by 1073

Abstract

Neuroblastoma (NB) is a childhood cancer, commonly treated with drugs, such as etoposide (ETO), whose efficacy is limited by the onset of resistance. Here, aiming at identifying new treatments for chemo-resistant NB, the effects of two synthesized imidazo-pyrazoles (IMPs) (4G and 4I) were investigated on ETO-sensitive (HTLA-230) and ETO-resistant (HTLA-ER) NB cells, detecting 4I as the more promising compound, that demonstrated IC₅₀ values lower than those of ETO on HTLA ER. Therefore, to further improve the activity of 4I, we developed 4I-loaded palmitic acid (PA) and polystyrene-based (P5) cationic nanoparticles (P5PA-4I NPs) with high drug loading (21%) and encapsulation efficiency (97%), by a single oil-in-water emulsification technique. Biocompatible PA was adopted as an emulsion stabilizer, while synthesized P5 acted as an encapsulating agent, solubilizer and hydrophilic–lipophilic balance (HLB) improver. Optic microscopy and cytofluorimetric analyses were performed to investigate the micromorphology, size and complexity distributions of P5PA-4I NPs, which were also structurally characterized by chemometric-assisted Fourier transform infrared spectroscopy (FTIR). Potentiometric titrations allowed us to estimate the milliequivalents of PA and basic nitrogen atoms present in NPs. P5PA-4I NPs afforded dispersions in water with excellent buffer capacity, essential to escape lysosomal degradation and promote long residence time inside cells. They were chemically stable in an aqueous medium for at least 40 days, while in dynamic light scattering (DLS) analyses, P5PA-4I showed a mean hydrodynamic diameter of 541 nm, small polydispersity (0.194), and low positive zeta potentials (+8.39 mV), assuring low haemolytic toxicity. Biological experiments on NB cells, demonstrated that P5PA-4I NPs induced ROS-dependent cytotoxic effects significantly higher than those of pristine 4I, showing a major efficacy compared to ETO in reducing cell viability in HTLA-ER cells. Collectively, this 4I-based nano-formulation could represent a new promising macromolecular platform to develop a new delivery system able to increase the cytotoxicity of the anticancer drugs. Full article

(This article belongs to the Special Issue New Advances on Photosensitiser or Inhibitors Molecules for Cancer Treatment)

► Show Figures

Figure 1

12 pages, 6415 KiB

Open AccessArticle

Design, Synthesis and Antitumor Activity of 1H-indazole-3-amine Derivatives

by Congyu Wang, Mei Zhu, Xuesha Long, Qin Wang, Zhenchao Wang and Guiping Ouyang

Int. J. Mol. Sci. 2023, 24(10), 8686; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24108686 - 12 May 2023

Cited by 2 | Viewed by 1516

Abstract

A series of indazole derivatives were designed and synthesized by molecular hybridization strategy, and these compounds were evaluated the inhibitory activities against human cancer cell lines of lung (A549), chronic myeloid leukemia (K562), prostate (PC-3), and hepatoma (Hep-G2) by methyl thiazolyl tetrazolium (MTT) colorimetric assay. Among these, compound 6o exhibited a promising inhibitory effect against the K562 cell line with the IC₅₀ (50% inhibition concentration) value of 5.15 µM, and this compound showed great selectivity for normal cell (HEK-293, IC₅₀ = 33.2 µM). Moreover, compound 6o was confirmed to affect apoptosis and cell cycle possibly by inhibiting Bcl2 family members and the p53/MDM2 pathway in a concentration-dependent manner. Overall, this study indicates that compound 6o could be a promising scaffold to develop an effective and low-toxic anticancer agent. Full article

(This article belongs to the Special Issue New Advances on Photosensitiser or Inhibitors Molecules for Cancer Treatment)

► Show Figures

Figure 1

16 pages, 3712 KiB

Open AccessArticle

Phototoxic Potential of Different DNA Intercalators for Skin Cancer Therapy: In Vitro Screening

by Thais P. Pivetta, Tânia Vieira, Jorge C. Silva, Paulo A. Ribeiro and Maria Raposo

Int. J. Mol. Sci. 2023, 24(6), 5602; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24065602 - 15 Mar 2023

Cited by 3 | Viewed by 1523

Abstract

Photodynamic therapy is a minimally invasive procedure used in the treatment of several diseases, including some types of cancer. It is based on photosensitizer molecules, which, in the presence of oxygen and light, lead to the formation of reactive oxygen species (ROS) and consequent cell death. The selection of the photosensitizer molecule is important for the therapy efficiency; therefore, many molecules such as dyes, natural products and metallic complexes have been investigated regarding their photosensitizing potential. In this work, the phototoxic potential of the DNA-intercalating molecules—the dyes methylene blue (MB), acridine orange (AO) and gentian violet (GV); the natural products curcumin (CUR), quercetin (QT) and epigallocatechin gallate (EGCG); and the chelating compounds neocuproine (NEO), 1,10-phenanthroline (PHE) and 2,2′-bipyridyl (BIPY)—were analyzed. The cytotoxicity of these chemicals was tested in vitro in non-cancer keratinocytes (HaCaT) and squamous cell carcinoma (MET1) cell lines. A phototoxicity assay and the detection of intracellular ROS were performed in MET1 cells. Results revealed that the IC₅₀ values of the dyes and curcumin in MET1 cells were lower than 30 µM, while the values for the natural products QT and EGCG and the chelating agents BIPY and PHE were higher than 100 µM. The IC₅₀ of MB and AO was greatly affected by irradiation when submitted to 640 nm and 457 nm light sources, respectively. ROS detection was more evident for cells treated with AO at low concentrations. In studies with the melanoma cell line WM983b, cells were more resistant to MB and AO and presented slightly higher IC₅₀ values, in line with the results of the phototoxicity assays. This study reveals that many molecules can act as photosensitizers, but the effect depends on the cell line and the concentration of the chemical. Finally, significant photosensitizing activity of acridine orange at low concentrations and moderate light doses was demonstrated. Full article

(This article belongs to the Special Issue New Advances on Photosensitiser or Inhibitors Molecules for Cancer Treatment)

► Show Figures

Figure 1

Journal Menu

Journal Browser

New Advances on Photosensitiser or Inhibitors Molecules for Cancer Treatment

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (5 papers)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI