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New Molecular Insights into Antimicrobial Photo-Treatments
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New Molecular Insights into Antimicrobial Photo-Treatments

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

Deadline for manuscript submissions: 20 October 2025 | Viewed by 9006

Special Issue Editor

Dr. Pietro Delcanale

E-Mail Website
Guest Editor
Department of Mathematical, Physical and Computer Sciences, University of Parma, 43124 Parma, Italy
Interests: photo-active molecules; fluorescence microscopy; nanomedicine; photodynamic inactivation

Special Issue Information

Dear Colleagues,

The recent COVID-19 pandemic highlighted the need for the identification of new and effective treatments against emerging health threats. The insurgence of new microbial infections, including the growing number of antibiotic-resistant bacterial species, calls for a renewed effort towards the development of antimicrobials that do not induce resistance in microorganisms. Antimicrobial photo-treatments, such as photodynamic inactivation (PDI), antimicrobial photo-thermal therapy (PTT) or blue/near UV light-induced inactivation, are regarded as a viable alternative to antibiotics in a large variety of cases.

We invite investigators who are active in the field to submit original research papers as well as review articles to this Special Issue, to highlight the realization and the use of molecular and nano-systems for antimicrobial photo-treaments, to provide new insights into the fundamental mechanisms of microbial photo-inactivation or to propose stimulating ideas and novel applications to expand the use of the methodology. Scientific contributions are expected to provide molecular-level information about the systems and/or the processes under study. The issue will focus on, but will not be limited to, the following aspects:

  • Fundamental mechanisms of PDI, PTT or UV light-based antimicrobial treatments;
  • New photo-activated materials, including molecules and nanomaterials;
  • New formulations of existing photo-activated agents;
  • Targeted photo-treatments against bacteria and viruses;
  • Photo-treatments exploiting endogenous molecules;
  • Visualization of functional photo-activated agents in situ with advanced microscopy;
  • Combination treatments with, e.g., antibiotics or antibodies;
  • Photo-activated molecular systems for industrial and large-scale applications.

Dr. Pietro Delcanale
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

  • photodynamic inactivation
  • photo-thermal therapy
  • photosensitization
  • antimicrobials
  • reactive oxygen species
  • photo-treatments
  • antibiotic resistance
  • singlet oxygen
  • antivirals

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Published Papers (5 papers)

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Research

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13 pages, 1623 KB  
Article
The Photodynamic Antibacterial Potential of New Tetracationic Zinc(II) Phthalocyanines Bearing 4-((Diethylmethylammonium)methyl)phenoxy Substituents
by Gennady Meerovich, Dmitry Bunin, Ekaterina Akhlyustina, Igor Romanishkin, Vladimir Levkin, Sergey Kharnas, Maria Stepanova, Alexander Martynov, Victor Loschenov, Yulia Gorbunova and Marina Strakhovskaya
Int. J. Mol. Sci. 2025, 26(19), 9414; https://doi.org/10.3390/ijms26199414 - 26 Sep 2025
Abstract
Photodynamic inactivation and antimicrobial photodynamic therapy (PDI/APDT) based on the toxic properties of reactive oxygen species (ROS), which are generated by a number of photoexcited dyes, are promising for preventing and treating infections, especially those associated with drug-resistant pathogens. The negatively charged bacterial [...] Read more.
Photodynamic inactivation and antimicrobial photodynamic therapy (PDI/APDT) based on the toxic properties of reactive oxygen species (ROS), which are generated by a number of photoexcited dyes, are promising for preventing and treating infections, especially those associated with drug-resistant pathogens. The negatively charged bacterial cell surface attracts polycationic photosensitizers, which contribute to the vulnerability of the bacterial plasma membrane to ROS. The integrity of the plasma membrane is critical for the viability of the bacterial cell. Polycationic phthalocyanines are regarded as promising photosensitizers due to their high quantum yields of ROS generation (mainly singlet oxygen), high extinction coefficients in the far-red spectral range, and low dark toxicity. For application in PDI/APDT, the wide range of possibilities of modifying the chemical structure of phthalocyanines is particularly valuable, especially by introducing various peripheral and non-peripheral substituents into the benzene rings. Depending on the type and location of such substituents, it is possible to obtain photosensitizers with different photophysical properties, photochemical activity, solubility in an aqueous medium, biocompatibility, and tropism for certain structures of photoinactivation targets. In this study, we tested novel water-soluble Zn (II) phthalocyanines bearing four 4-((diethylmethylammonium)methyl)phenoxy substituents with symmetric and asymmetric charge distributions for photodynamic antibacterial activity and compared them with those of water-soluble octacationic zinc octakis(cholinyl)phthalocyanine. The obtained results allow us to conclude that the studied tetracationic aryloxy-substituted Zn(II) phthalocyanines effectively bind to the oppositely charged cell wall of the Gram-negative bacteria E. coli. This finding is supported by data on bacteria’s zeta potential neutralization in the presence of phthalocyanine derivatives and fluorescence microscopy images of stained bacterial cells. Asymmetric substitution influences the aggregation and fluorescent characteristics but has little effect on the ability of the studied tetracationic phthalocyanines to sensitize the bioluminescent E. coli K12 TG1 strain. Both symmetric and asymmetric aryloxy-substituted phthalocyanines are no less effective in PDI than the water-soluble zinc octakis(cholinyl)phthalocyanine, a photosensitizer with proven antibacterial activity, and have significant potential for further studies as antibacterial photosensitizers. Full article
(This article belongs to the Special Issue New Molecular Insights into Antimicrobial Photo-Treatments)
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27 pages, 6077 KB  
Article
Photodynamic Effectiveness of Copper-Iminopyridine Photosensitizers Coupled to Zinc Oxide Nanoparticles Against Klebsiella pneumoniae and the Bacterial Response to Oxidative Stress
by Dafne Berenice Hormazábal, Ángeles Beatriz Reyes, Matías Fabián Cuevas, Angélica R. Bravo, David Moreno-da Costa, Iván A. González, Daniel Navas, Iván Brito, Paulina Dreyse, Alan R. Cabrera and Christian Erick Palavecino
Int. J. Mol. Sci. 2025, 26(9), 4178; https://doi.org/10.3390/ijms26094178 - 28 Apr 2025
Cited by 1 | Viewed by 855
Abstract
One of the most urgent threats to public health worldwide is the ongoing rise of multidrug-resistant (MDR) bacterial strains. Among the most critical pathogens are MDR-Klebsiella pneumoniae strains. The lack of new antibiotics has led to an increased need for non-antibiotic antimicrobial [...] Read more.
One of the most urgent threats to public health worldwide is the ongoing rise of multidrug-resistant (MDR) bacterial strains. Among the most critical pathogens are MDR-Klebsiella pneumoniae strains. The lack of new antibiotics has led to an increased need for non-antibiotic antimicrobial therapies. Photodynamic therapy (PDT) has become increasingly significant in treating MDR bacteria. PDT uses photosensitizer compounds (PS) that generate reactive oxygen species (ROS) when activated by light. These ROS produce localized oxidative stress, damaging the bacterial envelope. A downside of PDT is the limited bioavailability of PSs in vivo, which can be enhanced by conjugating them with carriers like nanoparticles (NPs). Zinc nanoparticles possess antibacterial properties, decreasing the adherence and viability of microorganisms on surfaces. The additive or synergistic effect of the combined NP-PS could improve phototherapeutic action. Therefore, this study evaluated the effectiveness of the copper(I)-based PS CuC1 compound in combination with Zinc Oxide NP, ZnONP, to inhibit the growth of both MDR and sensitive K. pneumoniae strains. The reduction in bacterial viability after exposure to a PS/NP mixture activated by 61.2 J/cm2 of blue light photodynamic treatment was assessed. The optimal PS/NP ratio was determined at 2 µg/mL of CuC1 combined with 64 µg/mL of ZnONP as the minimum effective concentration (MEC). The bacterial gene response aligned with a mechanism of photooxidative stress induced by the treatment, which damages the bacterial cell envelope. Additionally, we found that the PS/NP mixture is not harmful to mammalian cells, such as Hep-G2 and HEK-293. In conclusion, the CuC1/ZnONP combination could effectively aid in enhancing the antimicrobial treatment of infections caused by MDR bacteria. Full article
(This article belongs to the Special Issue New Molecular Insights into Antimicrobial Photo-Treatments)
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11 pages, 1507 KB  
Communication
Insights on the Mechanical Properties of SARS-CoV-2 Particles and the Effects of the Photosensitizer Hypericin
by Matteo Mariangeli, Ana Moreno, Pietro Delcanale, Stefania Abbruzzetti, Alberto Diaspro, Cristiano Viappiani and Paolo Bianchini
Int. J. Mol. Sci. 2024, 25(16), 8724; https://doi.org/10.3390/ijms25168724 - 10 Aug 2024
Cited by 2 | Viewed by 4287
Abstract
SARS-CoV-2 is a highly pathogenic virus responsible for the COVID-19 disease. It belongs to the Coronaviridae family, characterized by a phospholipid envelope, which is crucial for viral entry and replication in host cells. Hypericin, a lipophilic, naturally occurring photosensitizer, was reported to effectively [...] Read more.
SARS-CoV-2 is a highly pathogenic virus responsible for the COVID-19 disease. It belongs to the Coronaviridae family, characterized by a phospholipid envelope, which is crucial for viral entry and replication in host cells. Hypericin, a lipophilic, naturally occurring photosensitizer, was reported to effectively inactivate enveloped viruses, including SARS-CoV-2, upon light irradiation. In addition to its photodynamic activity, Hyp was found to exert an antiviral action also in the dark. This study explores the mechanical properties of heat-inactivated SARS-CoV-2 viral particles using Atomic Force Microscopy (AFM). Results reveal a flexible structure under external stress, potentially contributing to the virus pathogenicity. Although the fixation protocol causes damage to some particles, correlation with fluorescence demonstrates colocalization of partially degraded virions with their genome. The impact of hypericin on the mechanical properties of the virus was assessed and found particularly relevant in dark conditions. These preliminary results suggest that hypericin can affect the mechanical properties of the viral envelope, an effect that warrants further investigation in the context of antiviral therapies. Full article
(This article belongs to the Special Issue New Molecular Insights into Antimicrobial Photo-Treatments)
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18 pages, 3253 KB  
Article
Concanavalin A Delivers a Photoactive Protein to the Bacterial Wall
by Andrea Mussini, Pietro Delcanale, Melissa Berni, Stefano Pongolini, Mireia Jordà-Redondo, Montserrat Agut, Peter J. Steinbach, Santi Nonell, Stefania Abbruzzetti and Cristiano Viappiani
Int. J. Mol. Sci. 2024, 25(11), 5751; https://doi.org/10.3390/ijms25115751 - 25 May 2024
Cited by 6 | Viewed by 2297
Abstract
Modular supramolecular complexes, where different proteins are assembled to gather targeting capability and photofunctional properties within the same structures, are of special interest for bacterial photodynamic inactivation, given their inherent biocompatibility and flexibility. We have recently proposed one such structure, exploiting the tetrameric [...] Read more.
Modular supramolecular complexes, where different proteins are assembled to gather targeting capability and photofunctional properties within the same structures, are of special interest for bacterial photodynamic inactivation, given their inherent biocompatibility and flexibility. We have recently proposed one such structure, exploiting the tetrameric bacterial protein streptavidin as the main building block, to target S. aureus protein A. To expand the palette of targets, we have linked biotinylated Concanavalin A, a sugar-binding protein, to a methylene blue-labelled streptavidin. By applying a combination of spectroscopy and microscopy, we demonstrate the binding of Concanavalin A to the walls of Gram-positive S. aureus and Gram-negative E. coli. Photoinactivation is observed for both bacterial strains in the low micromolar range, although the moderate affinity for the molecular targets and the low singlet oxygen yields limit the overall efficiency. Finally, we apply a maximum entropy method to the analysis of autocorrelation traces, which proves particularly useful when interpreting signals measured for diffusing systems heterogeneous in size, such as fluorescent species bound to bacteria. Full article
(This article belongs to the Special Issue New Molecular Insights into Antimicrobial Photo-Treatments)
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Review

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28 pages, 2883 KB  
Review
Natural Biomolecules and Light: Antimicrobial Photodynamic Strategies in the Fight Against Antibiotic Resistance
by Greta Amendola, Mariagrazia Di Luca and Antonella Sgarbossa
Int. J. Mol. Sci. 2025, 26(16), 7993; https://doi.org/10.3390/ijms26167993 - 19 Aug 2025
Viewed by 668
Abstract
The alarming increase in infections caused by antimicrobial-resistant bacteria is increasingly posing a critical threat to public health. For this reason, the scientific community is focusing on alternative therapeutic strategies, such as antimicrobial photodynamic therapy (aPDT). This review examined the use of natural [...] Read more.
The alarming increase in infections caused by antimicrobial-resistant bacteria is increasingly posing a critical threat to public health. For this reason, the scientific community is focusing on alternative therapeutic strategies, such as antimicrobial photodynamic therapy (aPDT). This review examined the use of natural photosensitizers (PSs) in aPDT, emphasizing how they may produce high yields of reactive oxygen species when activated by light and consequently inactivate a wide range of pathogens, including bacteria embedded in biofilms, efficiently. The main methodologies and several strategies of incorporation into cutting-edge nanotechnological delivery systems of the most prevalent natural PSs (curcuminoids, perylenequinones, tetrapyrrolic macrocycles, and flavins) have been analyzed. Although natural PSs have benefits in terms of environmental sustainability and biocompatibility, their clinical use is frequently constrained by low bioavailability and solubility, issues that are being addressed more and more through novel formulations and dual-mode treatments. Studies conducted both in vitro and in vivo highlight these compounds’ strong antibacterial and wound-healing properties. In conclusion, natural molecule-based aPDT is a flexible and successful strategy for combating antimicrobial resistance, deserving of more translational study and clinical advancement. Full article
(This article belongs to the Special Issue New Molecular Insights into Antimicrobial Photo-Treatments)
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