Pub Date : 2025-02-27DOI: 10.1016/j.jphotobiol.2025.113137
Aoqing Jia , Min Zheng , Zhigang Xie
Due to inadequate light transmission into the subsurface, one of the key challenges for conventional photodynamic therapy (PDT) is realizing successful treatment of deep-skin pathogenetic bacterial infectious wounds. Preparation of near-infrared (NIR) photosensitizers (PSs) with potent antibacterial activity is a potential solution to address this issue. In the present work, a boron dipyrromethene (BDP) derivative was synthesized, which had red light absorption and NIR fluorescence. Under 635 nm of irradiation, BDP could generate massive reactive oxygen species (ROS) for sterilization, which exhibited robust photodynamic antiseptic property against Gram-positive bacteria (S. aureus), with a minimum inhibitory concentration of only 240 nM (140 mW cm −2). More importantly, BDP was capable of efficiently suppressing the development of bacterial biofilms and even eliminate established biofilms, thereby facilitating the enhancement of sterilizing efficacy. Furthermore, the promising antibacterial capability of BDP was validated in the treatment of S. aureus-infected abscess. The present work presents an antibiotic-free strategy for highly effective light-triggered abscess therapy.
{"title":"Boron dipyrromethene fungicide for anti-microbial photodynamic therapeutics","authors":"Aoqing Jia , Min Zheng , Zhigang Xie","doi":"10.1016/j.jphotobiol.2025.113137","DOIUrl":"10.1016/j.jphotobiol.2025.113137","url":null,"abstract":"<div><div>Due to inadequate light transmission into the subsurface, one of the key challenges for conventional photodynamic therapy (PDT) is realizing successful treatment of deep-skin pathogenetic bacterial infectious wounds. Preparation of near-infrared (NIR) photosensitizers (PSs) with potent antibacterial activity is a potential solution to address this issue. In the present work, a boron dipyrromethene (BDP) derivative was synthesized, which had red light absorption and NIR fluorescence. Under 635 nm of irradiation, BDP could generate massive reactive oxygen species (ROS) for sterilization, which exhibited robust photodynamic antiseptic property against Gram-positive bacteria (<em>S. aureus</em>), with a minimum inhibitory concentration of only 240 nM (140 mW cm <sup>−2</sup>). More importantly, BDP was capable of efficiently suppressing the development of bacterial biofilms and even eliminate established biofilms, thereby facilitating the enhancement of sterilizing efficacy. Furthermore, the promising antibacterial capability of BDP was validated in the treatment of <em>S. aureus</em>-infected abscess. The present work presents an antibiotic-free strategy for highly effective light-triggered abscess therapy.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"265 ","pages":"Article 113137"},"PeriodicalIF":3.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-25DOI: 10.1016/j.jphotobiol.2025.113136
Cailing Fan , Kaifu Ma , Ran Chen , Tianyu Zhang , Yonghao Song , Lei Liu , Weijie Chi , Qinxi Dong , Wei Shu , Chaoyuan Zeng
The inappropriate or excessive drug and alcohol consumption is a major cause of liver injuries. The development of a tool capable of visualizing the liver injury process with high precision, and in real time is particularly urgent. In this study, we designed and synthesized a novel HOCl-responsive fluorescent probe, PTZ-NS, for tracking mitochondrial HOCl during liver injury. PTZ-NS exhibits excellent sensitivity and selectivity for HOCl, with a detection limit of 158 nM. It can specifically target mitochondria, and successfully distinguishing between HepG2 and L-02 cells. The probe was also effective in tracking changes of endogenous HOCl levels in cells and zebrafish, and it was used to capture the increase in HOCl content during ferroptosis. Crucially, PTZ-NS was successfully employed to monitor HOCl during alcohol-induced liver disease (AID) and drug-induced liver injury (DILI) in mice liver tissue. Overall, PTZ-NS not only facilitate the real-time and precise observation of liver injury but also open up promising avenues for future disease prevention and research.
{"title":"Construction of a NIR fluorescent probe for tracking mitochondrial HOCl during liver injury","authors":"Cailing Fan , Kaifu Ma , Ran Chen , Tianyu Zhang , Yonghao Song , Lei Liu , Weijie Chi , Qinxi Dong , Wei Shu , Chaoyuan Zeng","doi":"10.1016/j.jphotobiol.2025.113136","DOIUrl":"10.1016/j.jphotobiol.2025.113136","url":null,"abstract":"<div><div>The inappropriate or excessive drug and alcohol consumption is a major cause of liver injuries. The development of a tool capable of visualizing the liver injury process with high precision, and in real time is particularly urgent. In this study, we designed and synthesized a novel HOCl-responsive fluorescent probe, <strong>PTZ-NS</strong>, for tracking mitochondrial HOCl during liver injury. <strong>PTZ-NS</strong> exhibits excellent sensitivity and selectivity for HOCl, with a detection limit of 158 nM. It can specifically target mitochondria, and successfully distinguishing between HepG2 and L-02 cells. The probe was also effective in tracking changes of endogenous HOCl levels in cells and zebrafish, and it was used to capture the increase in HOCl content during ferroptosis. Crucially, <strong>PTZ-NS</strong> was successfully employed to monitor HOCl during alcohol-induced liver disease (AID) and drug-induced liver injury (DILI) in mice liver tissue. Overall, <strong>PTZ-NS</strong> not only facilitate the real-time and precise observation of liver injury but also open up promising avenues for future disease prevention and research.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"265 ","pages":"Article 113136"},"PeriodicalIF":3.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-23DOI: 10.1016/j.jphotobiol.2025.113135
Tiantian Sun , Sijia Wang , Xiao Liu , Dongliang Ji , Xudong Xie , Ruiqi Yang , Lei Wang , Yong Ling , Chang-Chun Ling
Photodynamic therapy (PDT) is an emerging therapeutic modality to selectively eradicate pathological cells, such as cancer cells. Hence, we designed and synthesized a series of novel ꞵ-carboline/cyanoisoflavone photosensitizers A1-A3. All compounds possessed potent type-I/-II photodynamic properties. Especially, the optimized compound A2 produced large amounts of •O2−, •OH, and 1O2 under irradiation, and exhibited a higher quantum yield of singlet oxygen (ΦΔ = 0.92) than others. Furthermore, A2 not only exhibited potent cytotoxicity in HT29 cells, but also demonstrated prominent chemo-photodynamic effects with IC50 values of 3.9–4.1 μM under normoxic and hypoxic conditions in HT29 cells, while exhibited minimal toxicity to normal cells, suggesting its tumor-selective and hypoxia-tolerant efficacy. Most importantly, A2 significantly promoted mitochondrial damage and ferroptosis, through depleting GSH/GPX-4 levels and increasing malondialdehyde (MDA) expression. Finally, in vivo studies showed that A2 achieved a high colonic tumor-inhibitory rate of 84.6 % through chemo-photodynamic therapy. These findings provide a promising framework for the development of novel photosensitizers for chemo-photodynamic therapy.
{"title":"Novel ꞵ-carboline/cyanoisoflavone photosensitizers for ferroptosis-induced efficient chemo-photodynamic synergistic cancer therapy","authors":"Tiantian Sun , Sijia Wang , Xiao Liu , Dongliang Ji , Xudong Xie , Ruiqi Yang , Lei Wang , Yong Ling , Chang-Chun Ling","doi":"10.1016/j.jphotobiol.2025.113135","DOIUrl":"10.1016/j.jphotobiol.2025.113135","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) is an emerging therapeutic modality to selectively eradicate pathological cells, such as cancer cells. Hence, we designed and synthesized a series of novel ꞵ-carboline/cyanoisoflavone photosensitizers <strong>A1</strong>-<strong>A3</strong>. All compounds possessed potent type-I/-II photodynamic properties. Especially, the optimized compound <strong>A2</strong> produced large amounts of •O<sub>2</sub><sup>−</sup>, •OH, and <sup>1</sup>O<sub>2</sub> under irradiation, and exhibited a higher quantum yield of singlet oxygen (Φ<sub>Δ</sub> = 0.92) than others. Furthermore, <strong>A2</strong> not only exhibited potent cytotoxicity in HT29 cells, but also demonstrated prominent chemo-photodynamic effects with IC<sub>50</sub> values of 3.9–4.1 μM under normoxic and hypoxic conditions in HT29 cells, while exhibited minimal toxicity to normal cells, suggesting its tumor-selective and hypoxia-tolerant efficacy. Most importantly, <strong>A2</strong> significantly promoted mitochondrial damage and ferroptosis, through depleting GSH/GPX-4 levels and increasing malondialdehyde (MDA) expression. Finally, in vivo studies showed that <strong>A2</strong> achieved a high colonic tumor-inhibitory rate of 84.6 % through chemo-photodynamic therapy. These findings provide a promising framework for the development of novel photosensitizers for chemo-photodynamic therapy.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"265 ","pages":"Article 113135"},"PeriodicalIF":3.9,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-21DOI: 10.1016/j.jphotobiol.2025.113134
Varvara G. Kubenko, Vladimir A. Pomogaev, Andrey A. Buglak, Alexei I. Kononov
Pterins are naturally occurring compounds widespread in living organisms. 5,6,7,8-Tetrahydrobiopterin (H4Bip) is a cofactor of several key enzymes, including NO-synthases and phenylalanine hydroxylase, whereas tetrahydrocyanopterin is a photoreceptor molecule in cyanobacteria. In this regard, tetrahydropterins (H4pterins) photochemistry and photophysics have been attracting our attention. H4pterins photodegrade in presence of molecular oxygen yielding dihydropterins (H2pterins) and oxidized pterins. Meanwhile, the excited states dynamics of H4pterins on a femto- and picosecond time-scale remains unclear. To shed light on this area, we perform time-resolved spectroscopy of H4Bip using fluorescence up-conversion as well as transient absorption spectroscopy techniques along with TD-DFT non-adiabatic molecular dynamics. We show that the lowest H4Bip exited state has a lifetime of ca. 200 fs. Using the BHandHLYP functional and multireference spin-flip (MRSF) method we demonstrate that starting from the S4 state, H4Bip passes to the S1 state within 50 fs, and after 200 fs a conical intersection with the ground S0 state is achieved. As a whole, the excited state behavior of H4Bip is similar to DNA nucleobases, in particular guanine. These findings allow us to make some speculations about the biochemical role of H4pterins photophysics.
{"title":"Photophysics of 5,6,7,8-tetrahydrobiopterin on a femtosecond time-scale","authors":"Varvara G. Kubenko, Vladimir A. Pomogaev, Andrey A. Buglak, Alexei I. Kononov","doi":"10.1016/j.jphotobiol.2025.113134","DOIUrl":"10.1016/j.jphotobiol.2025.113134","url":null,"abstract":"<div><div>Pterins are naturally occurring compounds widespread in living organisms. 5,6,7,8-Tetrahydrobiopterin (H<sub>4</sub>Bip) is a cofactor of several key enzymes, including NO-synthases and phenylalanine hydroxylase, whereas tetrahydrocyanopterin is a photoreceptor molecule in cyanobacteria. In this regard, tetrahydropterins (H<sub>4</sub>pterins) photochemistry and photophysics have been attracting our attention. H<sub>4</sub>pterins photodegrade in presence of molecular oxygen yielding dihydropterins (H<sub>2</sub>pterins) and oxidized pterins. Meanwhile, the excited states dynamics of H<sub>4</sub>pterins on a femto- and picosecond time-scale remains unclear. To shed light on this area, we perform time-resolved spectroscopy of H<sub>4</sub>Bip using fluorescence up-conversion as well as transient absorption spectroscopy techniques along with TD-DFT non-adiabatic molecular dynamics. We show that the lowest H<sub>4</sub>Bip exited state has a lifetime of ca. 200 fs. Using the BHandHLYP functional and multireference spin-flip (MRSF) method we demonstrate that starting from the S<sub>4</sub> state, H<sub>4</sub>Bip passes to the S<sub>1</sub> state within 50 fs, and after 200 fs a conical intersection with the ground S<sub>0</sub> state is achieved. As a whole, the excited state behavior of H<sub>4</sub>Bip is similar to DNA nucleobases, in particular guanine. These findings allow us to make some speculations about the biochemical role of H<sub>4</sub>pterins photophysics.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"265 ","pages":"Article 113134"},"PeriodicalIF":3.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-20DOI: 10.1016/j.jphotobiol.2025.113133
Alysson Benite de Freitas , Hanstter Hallison Alves Rezende , Guilherme Rocha Lino de Souza , Pablo José Gonçalves
The global rise of difficult-to-treat resistance (DTR) bacteria, such as Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp), poses a critical challenge in controlling infections and curbing the spread of antimicrobial resistance genes. Antimicrobial photodynamic inactivation (aPDI) offers a promising alternative to traditional antimicrobials by effectively targeting extensively drug-resistant pathogens and mitigating antimicrobial resistance. This study investigated the in vitro photodynamic efficacy of the cationic porphyrin 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP) against planktonic cultures of KPC-Kp. The minimum effective concentration (MEC) of TMPyP for significant photodynamic activity was determined to be 0.8 μM under an irradiance of 314 ± 11 mW/cm2, delivering a total light dose of 189 J/cm2. At the same concentration, bacterial suspensions exposed to a lower irradiance of 107 ± 7 mW/cm2 achieved a > 99.997 % reduction in viability with a lethal light dose of 51.4 J/cm2. Scanning electron microscopy (SEM) revealed oxidative damage to the bacterial cell wall induced by aPDI. Hemolysis assays confirmed the safety of TMPyP, with no significant cytotoxicity or photocytotoxicity observed, and a selectivity index (SI) greater than 8, indicating a favorable therapeutic window. These findings underscore the potential of TMPyP-based aPDI as a therapeutic strategy to combat KPC-Kp infections. Further studies are warranted to explore its clinical applications and optimize treatment protocols for DTR bacterial infections.
{"title":"Photodynamic inactivation of KPC-producing Klebsiella pneumoniae difficult-to-treat resistance (DTR) by a cationic porphyrin","authors":"Alysson Benite de Freitas , Hanstter Hallison Alves Rezende , Guilherme Rocha Lino de Souza , Pablo José Gonçalves","doi":"10.1016/j.jphotobiol.2025.113133","DOIUrl":"10.1016/j.jphotobiol.2025.113133","url":null,"abstract":"<div><div>The global rise of difficult-to-treat resistance (DTR) bacteria, such as <em>Klebsiella pneumoniae</em> carbapenemase-producing <em>Klebsiella pneumoniae</em> (KPC-Kp), poses a critical challenge in controlling infections and curbing the spread of antimicrobial resistance genes. Antimicrobial photodynamic inactivation (aPDI) offers a promising alternative to traditional antimicrobials by effectively targeting extensively drug-resistant pathogens and mitigating antimicrobial resistance. This study investigated the <em>in vitro</em> photodynamic efficacy of the cationic porphyrin 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP) against planktonic cultures of KPC-Kp. The minimum effective concentration (MEC) of TMPyP for significant photodynamic activity was determined to be 0.8 μM under an irradiance of 314 ± 11 mW/cm<sup>2</sup>, delivering a total light dose of 189 J/cm<sup>2</sup>. At the same concentration, bacterial suspensions exposed to a lower irradiance of 107 ± 7 mW/cm<sup>2</sup> achieved a > 99.997 % reduction in viability with a lethal light dose of 51.4 J/cm<sup>2</sup>. Scanning electron microscopy (SEM) revealed oxidative damage to the bacterial cell wall induced by aPDI. Hemolysis assays confirmed the safety of TMPyP, with no significant cytotoxicity or photocytotoxicity observed, and a selectivity index (SI) greater than 8, indicating a favorable therapeutic window. These findings underscore the potential of TMPyP-based aPDI as a therapeutic strategy to combat KPC-Kp infections. Further studies are warranted to explore its clinical applications and optimize treatment protocols for DTR bacterial infections.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"265 ","pages":"Article 113133"},"PeriodicalIF":3.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-19DOI: 10.1016/j.jphotobiol.2025.113126
Pushpamali De Silva , Mohammad A. Saad , Joseph W.R. Swain , Zhiming Mai , Madeline D. Kidd , Joanna J. Choe , Assiris P. Camargo , Sanjay Anand , Vinay Chandrasekhara , Brian W. Pogue , Kenneth K. Wang , Bryan Q. Spring , Edward V. Maytin , Tayyaba Hasan
The poor response of pancreatic ductal adenocarcinoma (PDAC) to treatment, including immunotherapy, is attributed to its tumor microenvironment (TME). An ongoing challenge is the desmoplastic and immunosuppressed TME that evades immune surveillance. Here, we investigate transient modulation of the TME to overcome immunosuppression using a light-activated process, termed photodynamic priming (PDP). As a first step, this study captures the temporal dynamics of variations in immune infiltrates and subsequent immune responses in the TME, spleen, and blood of the KPC mouse model of PDAC post-PDP. In response to PDP, there were transient increases in tumor infiltrating lymphocytes (TIL) in tumors. The TIL population post-PDP includes an enrichment of CD8+ T cells, accompanied by temporal increases in PD-1, CTLA-4, and TIM-3 immune checkpoints on both CD8+ T and CD4+ T cells. Significant increases in CD11C+MHC-11+ dendritic cells and proliferating lymphocytes are observed in the spleen within several hours post-tumor PDP, suggesting initiation of adaptive immune responses. These observations are followed by an expansion of CD44+CD62−CD8+ effector memory T cells in the blood over several days as evidence of a systemic immune response. Post-PDP TME alterations also included the reduced formation of blood (CD31+) and lymphatic (Lyve-1+) vessels as well as decreases in PD-L1 and collagen content. Collectively, these data suggest that PDP helps to mitigate immunosuppressive mechanisms and promote enhanced tumor permeability. The temporal dynamics of the processes elucidated here pave the way to develop strategies in future work for combined PDP–immunotherapy utilizing the immune checkpoint expression dynamics for precision therapy.
{"title":"Photodynamic priming with red light triggers adaptive immune responses in a pancreatic cancer mouse model","authors":"Pushpamali De Silva , Mohammad A. Saad , Joseph W.R. Swain , Zhiming Mai , Madeline D. Kidd , Joanna J. Choe , Assiris P. Camargo , Sanjay Anand , Vinay Chandrasekhara , Brian W. Pogue , Kenneth K. Wang , Bryan Q. Spring , Edward V. Maytin , Tayyaba Hasan","doi":"10.1016/j.jphotobiol.2025.113126","DOIUrl":"10.1016/j.jphotobiol.2025.113126","url":null,"abstract":"<div><div>The poor response of pancreatic ductal adenocarcinoma (PDAC) to treatment, including immunotherapy, is attributed to its tumor microenvironment (TME). An ongoing challenge is the desmoplastic and immunosuppressed TME that evades immune surveillance. Here, we investigate transient modulation of the TME to overcome immunosuppression using a light-activated process, termed photodynamic priming (PDP). As a first step, this study captures the temporal dynamics of variations in immune infiltrates and subsequent immune responses in the TME, spleen, and blood of the KPC mouse model of PDAC post-PDP. In response to PDP, there were transient increases in tumor infiltrating lymphocytes (TIL) in tumors. The TIL population post-PDP includes an enrichment of CD8<sup>+</sup> T cells, accompanied by temporal increases in PD-1, CTLA-4, and TIM-3 immune checkpoints on both CD8<sup>+</sup> T and CD4<sup>+</sup> T cells. Significant increases in CD11C<sup>+</sup>MHC-11<sup>+</sup> dendritic cells and proliferating lymphocytes are observed in the spleen within several hours post-tumor PDP, suggesting initiation of adaptive immune responses. These observations are followed by an expansion of CD44<sup>+</sup>CD62<sup>−</sup>CD8<sup>+</sup> effector memory T cells in the blood over several days as evidence of a systemic immune response. Post-PDP TME alterations also included the reduced formation of blood (CD31<sup>+</sup>) and lymphatic (Lyve-1<sup>+</sup>) vessels as well as decreases in PD-L1 and collagen content. Collectively, these data suggest that PDP helps to mitigate immunosuppressive mechanisms and promote enhanced tumor permeability. The temporal dynamics of the processes elucidated here pave the way to develop strategies in future work for combined PDP–immunotherapy utilizing the immune checkpoint expression dynamics for precision therapy.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"265 ","pages":"Article 113126"},"PeriodicalIF":3.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-13DOI: 10.1016/j.jphotobiol.2025.113125
Ding Luo , Yanhong Mao , Shengni Zhang , Shengqiang Shen , Xiaohu Ge , Litao Zhang
It is widely recognized that ultraviolet (UV) radiation primarily catalyses photodamage in the skin by generating reactive oxygen species (ROS). In this study, we developed a novel antioxidant complex, Exo-SS31, by loading the antioxidant peptide SS31 (also known as MTP-131, elamipretide) into milk-derived exosomes. Our findings indicate that Exo-SS31 is an effective antioxidant capable of mitigating Human dermal fibroblast (HDF) damage induced by ultraviolet exposure, suppressing ROS production, and achieving greater therapeutic efficacy than SS31 alone. This complex can regulate the levels of superoxide dismutase (SOD) and glutathione (GSH) within the skin, inhibit the expression of proteins in pathways such as pMAPK and AP-1 triggered by UV radiation, and reduce the expression of the matrix metalloproteinases MMP1 and MMP3. Through these mechanisms, Exo-SS31 effectively prevents collagen degradation in the dermis and inhibits ultraviolet-induced photodamage. The use of milk-derived exosomes as carriers for antioxidant peptides represents a promising strategy to increase the bioavailability of peptide-based therapeutics.
{"title":"Milk-derived exosome-loaded SS31 as a novel strategy to mitigate UV-induced photodamage in skin","authors":"Ding Luo , Yanhong Mao , Shengni Zhang , Shengqiang Shen , Xiaohu Ge , Litao Zhang","doi":"10.1016/j.jphotobiol.2025.113125","DOIUrl":"10.1016/j.jphotobiol.2025.113125","url":null,"abstract":"<div><div>It is widely recognized that ultraviolet (UV) radiation primarily catalyses photodamage in the skin by generating reactive oxygen species (ROS). In this study, we developed a novel antioxidant complex, Exo-SS31, by loading the antioxidant peptide SS31 (also known as MTP-131, elamipretide) into milk-derived exosomes. Our findings indicate that Exo-SS31 is an effective antioxidant capable of mitigating Human dermal fibroblast (HDF) damage induced by ultraviolet exposure, suppressing ROS production, and achieving greater therapeutic efficacy than SS31 alone. This complex can regulate the levels of superoxide dismutase (SOD) and glutathione (GSH) within the skin, inhibit the expression of proteins in pathways such as pMAPK and AP-1 triggered by UV radiation, and reduce the expression of the matrix metalloproteinases MMP1 and MMP3. Through these mechanisms, Exo-SS31 effectively prevents collagen degradation in the dermis and inhibits ultraviolet-induced photodamage. The use of milk-derived exosomes as carriers for antioxidant peptides represents a promising strategy to increase the bioavailability of peptide-based therapeutics.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"265 ","pages":"Article 113125"},"PeriodicalIF":3.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-12DOI: 10.1016/j.jphotobiol.2025.113124
Haitao Chen , Changyou Chen , Haoyu Zhao , Yuanyuan Wei , Pingping Wang , Long-Fei Wu , Tao Song
Magnetotactic bacteria (MTB), known for their precision in navigating along magnetic fields, also exhibit light-sensitive behaviors. In Magnetospirillum magneticum AMB-1, the photoreceptor Amb2291 is involved in phototaxis regulation and magnetosome synthesis, particularly under oxidative stress. The magnetoreceptor Amb0994 modulates flagellar activity in response to magnetic field changes. Our study used a magneto-optical system to analyze the U-turn motility of north-seeking AMB-1 wild type (WT), amb2291 and amb0994 mutants under reversed magnetic fields and controlled light conditions. The results showed that WT strains consistently executed U-turns in response to magnetic fields, regardless of light variations. The diameters of U-turn of amb0994 mutant were smaller than those of the WT control. When illuminated with blue light in a direction opposite to the magnetic field, Δamb0994 exhibited slower U-turns with diameters similar to WT. In contrast, the Δamb2291 strain exhibited exaggerated U-turn movements under blue light, characterized by larger movement diameters and times compared to the WT, particularly whatever the light propagation direction is the same or opposite to the magnetic field in the initial state of motility. Gene expression analysis revealed that long-term exposure to blue light and magnetic fields led to a significant upregulation of amb2291 in Δamb0994 mutant strains and amb0994 in Δamb2291 mutant strains. These indicate a potential cooperative role of amb2291 and amb0994 in modulating bacterial motility under blue light. This research enhances our understanding of photoreception in MTB and its impact on magnetotaxis, shedding light on how environmental factors interact with microorganisms.
{"title":"Synergistic mechanism of magneto-optical sensing mediated by magnetic response protein Amb0994 and LOV-like protein Amb2291 in Magnetospirillum magneticum AMB-1","authors":"Haitao Chen , Changyou Chen , Haoyu Zhao , Yuanyuan Wei , Pingping Wang , Long-Fei Wu , Tao Song","doi":"10.1016/j.jphotobiol.2025.113124","DOIUrl":"10.1016/j.jphotobiol.2025.113124","url":null,"abstract":"<div><div>Magnetotactic bacteria (MTB), known for their precision in navigating along magnetic fields, also exhibit light-sensitive behaviors. In <em>Magnetospirillum magneticum</em> AMB-1, the photoreceptor Amb2291 is involved in phototaxis regulation and magnetosome synthesis, particularly under oxidative stress. The magnetoreceptor Amb0994 modulates flagellar activity in response to magnetic field changes. Our study used a magneto-optical system to analyze the U-turn motility of north-seeking AMB-1 wild type (WT), <em>amb2291</em> and <em>amb0994</em> mutants under reversed magnetic fields and controlled light conditions. The results showed that WT strains consistently executed U-turns in response to magnetic fields, regardless of light variations. The diameters of U-turn of <em>amb0994</em> mutant were smaller than those of the WT control. When illuminated with blue light in a direction opposite to the magnetic field, Δ<em>amb0994</em> exhibited slower U-turns with diameters similar to WT. In contrast, the Δ<em>amb2291</em> strain exhibited exaggerated U-turn movements under blue light, characterized by larger movement diameters and times compared to the WT, particularly whatever the light propagation direction is the same or opposite to the magnetic field in the initial state of motility. Gene expression analysis revealed that long-term exposure to blue light and magnetic fields led to a significant upregulation of <em>amb2291</em> in Δ<em>amb0994</em> mutant strains and <em>amb0994</em> in Δ<em>amb2291</em> mutant strains. These indicate a potential cooperative role of <em>amb2291</em> and <em>amb0994</em> in modulating bacterial motility under blue light. This research enhances our understanding of photoreception in MTB and its impact on magnetotaxis, shedding light on how environmental factors interact with microorganisms.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"265 ","pages":"Article 113124"},"PeriodicalIF":3.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143421944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The novel approach for fast comparative evaluation of the potency of new photosensitizers using model lipid membranes is described and substantiated. For this purpose, mixed Langmuir monolayers and Langmuir-Blodgett films containing one of the typical relatively easy photodegradable lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and one of the examined photosensitizers (PSs) are proposed as the models. The changes in the macroscopic properties of such model PS + POPC membranes upon irradiation with visible light (the photo-destruction processes) were recorded using two different methods: commonly used water contact angle measurements and new express method based on the estimation of the changes of the model mixed monolayer mechanical characteristics. The study have been carried out for two series of PSs, cationic and neutral ones. The results of water contact angel measurements have clearly demonstrated that this method can be used for studying the photodestruction of artificial lipid membranes on solid substrates and for comparison of the efficiency of new PSs. However, since model making and measurements are complex and time-consuming, it restricts the preliminary analysis of PSs efficiency. In this work, we suggest rather a simple method for the rapid comparative evaluation of new PSs based on easy and fast measurements, such as recording the surface pressure during irradiation of a PS-containing monolayer directly at an aqueous subphase and determining the mechanical properties of a model monolayer by the oscillating barrier method. The results have demonstrated that the proposed methods are quite valid for studying the photodegradation of artificial lipid membranes and comparing the efficiency of new PSs. In particular, we have shown that these methods can be used not only for multiparametric monitoring of the photodegradation kinetics but also for comparing the efficiency of PSs in lipid structures. The universality of the proposed methods for assessing the effectiveness of PDT at the use of PSs of various structures was demonstrated. The results of this study indicate that cationic PSs exhibit superior activity compared to neutral and anionic ones.
{"title":"Novel approach for fast comparative evaluation of the potency of new photosensitizers using model lipid membranes","authors":"Daria Danilova , Petr Ostroverkhov , Dmitry Medvedev , Mikhail Grin , Sofiya Selektor","doi":"10.1016/j.jphotobiol.2025.113123","DOIUrl":"10.1016/j.jphotobiol.2025.113123","url":null,"abstract":"<div><div>The novel approach for fast comparative evaluation of the potency of new photosensitizers using model lipid membranes is described and substantiated. For this purpose, mixed Langmuir monolayers and Langmuir-Blodgett films containing one of the typical relatively easy photodegradable lipid 1-palmitoyl-2-oleoyl-<em>sn</em>-glycero-3-phosphocholine (POPC) and one of the examined photosensitizers (PSs) are proposed as the models. The changes in the macroscopic properties of such model PS + POPC membranes upon irradiation with visible light (the photo-destruction processes) were recorded using two different methods: commonly used water contact angle measurements and new express method based on the estimation of the changes of the model mixed monolayer mechanical characteristics. The study have been carried out for two series of PSs, cationic and neutral ones. The results of water contact angel measurements have clearly demonstrated that this method can be used for studying the photodestruction of artificial lipid membranes on solid substrates and for comparison of the efficiency of new PSs. However, since model making and measurements are complex and time-consuming, it restricts the preliminary analysis of PSs efficiency. In this work, we suggest rather a simple method for the rapid comparative evaluation of new PSs based on easy and fast measurements, such as recording the surface pressure during irradiation of a PS-containing monolayer directly at an aqueous subphase and determining the mechanical properties of a model monolayer by the oscillating barrier method. The results have demonstrated that the proposed methods are quite valid for studying the photodegradation of artificial lipid membranes and comparing the efficiency of new PSs. In particular, we have shown that these methods can be used not only for multiparametric monitoring of the photodegradation kinetics but also for comparing the efficiency of PSs in lipid structures. The universality of the proposed methods for assessing the effectiveness of PDT at the use of PSs of various structures was demonstrated. The results of this study indicate that cationic PSs exhibit superior activity compared to neutral and anionic ones.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"265 ","pages":"Article 113123"},"PeriodicalIF":3.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Skin photoaging caused by ultraviolet rays (UVR) not only affects the appearance, but also leads to benign and malignant skin tumors. Vicenin-2, a bioflavonoid, exhibits anti-UVB properties, but its potential in preventing skin photoaging and the underlying mechanisms remain unclear. This study aims to elucidate the molecular mechanisms of Vicenin-2 in treating photoaging through network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation.
Methods
We utilized PubChem, Swiss Target Prediction, and Target Net databases to obtain the action targets of Vicenin-2. The Online Mendelian Inheritance in Man (OMIM), GeneCards, and Therapeutic Target Database (TTD) databases were employed to hunt for photoaging-related targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted via the Metascape database. Molecular docking and dynamics simulation methods were used for analyzing the binding sites and binding energies between Vicenin-2 and photoaging targets. Then, a photoaging mouse model and a Human foreskin fibroblast cells (HFF-1) model were created, the therapeutic effect and molecular mechanism of action of Vicenin-2 were validated by Hematoxylin and eosin (H&E), Masson staining and Elastica-Van Gieson (EVG) Staining, enzyme-linked immunosorbent assay (ELISA), Western blot (WB), Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) Assay, Antioxidant enzyme activities and quantitative reverse transcription-polymerase chain reaction (qRT-PCR).
Result
The screening of chemical composition and targets indicated that 249 genetic targets of Vicenin-2 were related to photoaging. Bioinformatics analysis suggested that Matrix Metalloproteinases 9(MMP9), Glycogen Synthase Kinase 3(GSK3β), Heat Shock Protein 90 AA1(HSP90AA1) and Nuclear Factor kappa-B1(NF-κB1) might be potential targets for Vicenin-2 in photoaging therapy. Molecular docking and dynamics simulation further showed that Vicenin-2 had the best binding to GSK3β. Through experimental verification, it has been demonstrated that Vicenin-2 alleviate photoaging, acting on GSK3β to regulate the phosphatidylinositol 3- kinase/serine-threonione kinase (PI3K/Akt) pathways, by reducing inflammation and apoptosis.
Conclusions
Vicenin-2 has anti-inflammatory and apoptosis-reducing effects through the action of multiple targets to relieve skin photoaging. Among them, GSK3β is the validated therapeutic target of Vicenin-2, which provides new ideas and clues for the development of photoaging therapy.
{"title":"Vicenin-2 reduces inflammation and apoptosis to relieve skin photoaging via suppressing GSK3β","authors":"Xinru Hu , Meng Chen , Bowen Tan, Hao Yang, Shanyong Li, Rucheng Li, Xinyu Zhang, Feng Long, Yinghao Huang, Xi Duan","doi":"10.1016/j.jphotobiol.2025.113117","DOIUrl":"10.1016/j.jphotobiol.2025.113117","url":null,"abstract":"<div><h3>Background</h3><div>Skin photoaging caused by ultraviolet rays (UVR) not only affects the appearance, but also leads to benign and malignant skin tumors. Vicenin-2, a bioflavonoid, exhibits anti-UVB properties, but its potential in preventing skin photoaging and the underlying mechanisms remain unclear. This study aims to elucidate the molecular mechanisms of Vicenin-2 in treating photoaging through network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation.</div></div><div><h3>Methods</h3><div>We utilized PubChem, Swiss Target Prediction, and Target Net databases to obtain the action targets of Vicenin-2. The Online Mendelian Inheritance in Man (OMIM), GeneCards, and Therapeutic Target Database (TTD) databases were employed to hunt for photoaging-related targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted via the Metascape database. Molecular docking and dynamics simulation methods were used for analyzing the binding sites and binding energies between Vicenin-2 and photoaging targets. Then, a photoaging mouse model and a Human foreskin fibroblast cells (HFF-1) model were created, the therapeutic effect and molecular mechanism of action of Vicenin-2 were validated by Hematoxylin and eosin (H&E), Masson staining and Elastica-Van Gieson (EVG) Staining, enzyme-linked immunosorbent assay (ELISA), Western blot (WB), Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) Assay, Antioxidant enzyme activities and quantitative reverse transcription-polymerase chain reaction (qRT-PCR).</div></div><div><h3>Result</h3><div>The screening of chemical composition and targets indicated that 249 genetic targets of Vicenin-2 were related to photoaging. Bioinformatics analysis suggested that Matrix Metalloproteinases 9(MMP9), Glycogen Synthase Kinase 3(GSK3β), Heat Shock Protein 90 AA1(HSP90AA1) and Nuclear Factor kappa-B1(NF-κB1) might be potential targets for Vicenin-2 in photoaging therapy. Molecular docking and dynamics simulation further showed that Vicenin-2 had the best binding to GSK3β. Through experimental verification, it has been demonstrated that Vicenin-2 alleviate photoaging, acting on GSK3β to regulate the phosphatidylinositol 3- kinase/serine-threonione kinase (PI3K/Akt) pathways, by reducing inflammation and apoptosis.</div></div><div><h3>Conclusions</h3><div>Vicenin-2 has anti-inflammatory and apoptosis-reducing effects through the action of multiple targets to relieve skin photoaging. Among them, GSK3β is the validated therapeutic target of Vicenin-2, which provides new ideas and clues for the development of photoaging therapy.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"264 ","pages":"Article 113117"},"PeriodicalIF":3.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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