The development of a simple drug formulation capable of achieving both activatable type I photoreaction and tumor-responsive release of immunomodulator is crucial for advancing photodynamic immunotherapy (PDIT). Herein, we present a nanostructured photosensitizer (NP5) that is activated by the acidic tumor microenvironment to produce type I reactive oxygen species (ROS) under light irradiation and release the immunomodulator demethylcantharidin (DMC) for PDIT. The NP5 is formed by self-assembly of a versatile phthalocyanine molecule which is composed of DMC and phthalocyanine linked via a pH-responsive amide bond. NP5 produces minimal ROS under light irradiation at the condition of pH 7.4. However, NP5 can release DMC at the condition of pH 6.5 and concurrently trigger type I photoreactions. The results of in vivo experiments indicate that NP5-mediated PDIT induce the increase of cytotoxic T lymphocytes and decrease of regulatory T lymphocytes, which can effectively inhibit the bilateral tumor growth. This work is anticipated to serve as a reference for the development of innovative agents for precise PDIT of hypoxic tumors.
开发一种既能实现可激活的 I 型光反应又能释放肿瘤反应性免疫调节剂的简单药物制剂对于推进光动力免疫疗法（PDIT）至关重要。在本文中，我们介绍了一种纳米结构光敏剂（NP5），它能被酸性肿瘤微环境激活，在光照射下产生 I 型活性氧（ROS），并释放出免疫调节剂去甲蒽醌（DMC），用于光动力免疫疗法。NP5 由多功能酞菁分子自组装而成，该分子由 DMC 和酞菁通过 pH 响应酰胺键连接而成。在 pH 值为 7.4 的条件下，NP5 在光照射下产生的 ROS 极少。然而，在 pH 值为 6.5 的条件下，NP5 可以释放 DMC 并同时引发 I 型光反应。体内实验结果表明，NP5 介导的 PDIT 能诱导细胞毒性 T 淋巴细胞的增加和调节性 T 淋巴细胞的减少，从而有效抑制双侧肿瘤的生长。这项研究有望为开发用于缺氧性肿瘤精确PDIT的创新药物提供参考。
{"title":"A tumor-pH-responsive phthalocyanine as activatable type I photosensitizer for improved photodynamic immunotherapy","authors":"Ling Zhang , Rong-Bin Que , Ting-Ting Ke, Chao Wang, Wei Xie, Hong-Jie Sun, Bi-Yuan Zheng, Mei-Rong Ke, Jian-Dong Huang, Xingshu Li","doi":"10.1016/j.jphotobiol.2024.113067","DOIUrl":"10.1016/j.jphotobiol.2024.113067","url":null,"abstract":"<div><div>The development of a simple drug formulation capable of achieving both activatable type I photoreaction and tumor-responsive release of immunomodulator is crucial for advancing photodynamic immunotherapy (PDIT). Herein, we present a nanostructured photosensitizer (NP5) that is activated by the acidic tumor microenvironment to produce type I reactive oxygen species (ROS) under light irradiation and release the immunomodulator demethylcantharidin (DMC) for PDIT. The NP5 is formed by self-assembly of a versatile phthalocyanine molecule which is composed of DMC and phthalocyanine linked <em>via</em> a pH-responsive amide bond. NP5 produces minimal ROS under light irradiation at the condition of pH 7.4. However, NP5 can release DMC at the condition of pH 6.5 and concurrently trigger type I photoreactions. The results of <em>in vivo</em> experiments indicate that NP5-mediated PDIT induce the increase of cytotoxic T lymphocytes and decrease of regulatory T lymphocytes, which can effectively inhibit the bilateral tumor growth. This work is anticipated to serve as a reference for the development of innovative agents for precise PDIT of hypoxic tumors.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"261 ","pages":"Article 113067"},"PeriodicalIF":3.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693184","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 : 2024-11-13DOI: 10.1016/j.jphotobiol.2024.113066
Shalini Dyagala , Sayantan Halder , Rishika Aggrawal , Milan Paul , Vinod K Aswal , Swati Biswas , Subit Kumar Saha
Hybrid nanoparticles formed by Silica (SiO2) coated with cationic gemini surfactants with variable hydroxyl group substituted spacers, 12-4(OH)-12,2Br− and 12-4(OH)2-12,2Br− have shown a great extent of compaction of calf thymus DNA (ct-DNA) compared to conventional counterpart cationic surfactant, dodecyl trimethylammonium bromide (DTAB). Study shows not only the hydrophobicity of the spacer but also the hydrogen bonding interactions between the hydroxyl group substituted spacer and DNA have a great role in DNA compaction. 12-4(OH)2-12,2Br− is more efficient in compacting ct-DNA compared to 12-4(OH)-12,2Br− due to the stronger binding of the former with ct-DNA than the latter. While 12-4(OH)-12,2Br− makes 50 % ct-DNA compaction at its 0.63 μM concentration in the presence of SiO2 nanoparticles, the same % of compaction can be achieved at a concentration as low as 0.25 μM of 12-4(OH)2-12,2Br−. However, DTAB makes 50 % ct-DNA compaction at a concentration as high as 7.00 μM under the same condition. Therefore, the present systems address the very common challenge, i.e., cytotoxicity due to cationic surfactants. The system of 12-4(OH)2-12,2Br− coated SiO2 nanoparticles displays the maximum cell viability (≥90 %), causing the least cell death in the mouse fibroblast cells (NIH3T3) cell lines compared to the cell viability of ≤80 % for DTAB. 12-4(OH)2-12,2Br− coated SiO2 nanoparticles system has presented excellent in vitro cellular uptake of genes on mouse mammary gland adenocarcinoma (4T1) cells after incubating for 3 h and 6 h. In vivo study shows that 12-4(OH)2-12,2Br− coated SiO2 nanoparticles system takes the highest amount of ct-DNA in cells and tumors in a time-dependent manner. The ex vivo studies using different organs of the mice demonstrate that the tumor sites in the breast of the mice are most affected by these formulations. Cytotoxicity assays and cellular uptake studies suggest that the present systems can be used for potential applications for gene delivery and oncological therapies.
{"title":"ct-DNA compaction by nanoparticles formed by silica and gemini surfactants having hydroxyl group substituted spacers: In vitro, in vivo, and ex vivo gene uptake to cancer cells","authors":"Shalini Dyagala , Sayantan Halder , Rishika Aggrawal , Milan Paul , Vinod K Aswal , Swati Biswas , Subit Kumar Saha","doi":"10.1016/j.jphotobiol.2024.113066","DOIUrl":"10.1016/j.jphotobiol.2024.113066","url":null,"abstract":"<div><div>Hybrid nanoparticles formed by Silica (SiO<sub>2</sub>) coated with cationic gemini surfactants with variable hydroxyl group substituted spacers, 12-4(OH)-12,2Br<sup>−</sup> and 12-4(OH)<sub>2</sub>-12,2Br<sup>−</sup> have shown a great extent of compaction of calf thymus DNA (ct-DNA) compared to conventional counterpart cationic surfactant, dodecyl trimethylammonium bromide (DTAB). Study shows not only the hydrophobicity of the spacer but also the hydrogen bonding interactions between the hydroxyl group substituted spacer and DNA have a great role in DNA compaction. 12-4(OH)<sub>2</sub>-12,2Br<sup>−</sup> is more efficient in compacting ct-DNA compared to 12-4(OH)-12,2Br<sup>−</sup> due to the stronger binding of the former with ct-DNA than the latter. While 12-4(OH)-12,2Br<sup>−</sup> makes 50 % ct-DNA compaction at its 0.63 μM concentration in the presence of SiO<sub>2</sub> nanoparticles, the same % of compaction can be achieved at a concentration as low as 0.25 μM of 12-4(OH)<sub>2</sub>-12,2Br<sup>−</sup>. However, DTAB makes 50 % ct-DNA compaction at a concentration as high as 7.00 μM under the same condition. Therefore, the present systems address the very common challenge, <em>i.e.</em>, cytotoxicity due to cationic surfactants. The system of 12-4(OH)<sub>2</sub>-12,2Br<sup>−</sup> coated SiO<sub>2</sub> nanoparticles displays the maximum cell viability (≥90 %), causing the least cell death in the mouse fibroblast cells (NIH3T3) cell lines compared to the cell viability of ≤80 % for DTAB. 12-4(OH)<sub>2</sub>-12,2Br<sup>−</sup> coated SiO<sub>2</sub> nanoparticles system has presented excellent <em>in vitro</em> cellular uptake of genes on mouse mammary gland adenocarcinoma (4T1) cells after incubating for 3 h and 6 h. <em>In vivo</em> study shows that 12-4(OH)<sub>2</sub>-12,2Br<sup>−</sup> coated SiO<sub>2</sub> nanoparticles system takes the highest amount of ct-DNA in cells and tumors in a time-dependent manner. The <em>ex vivo</em> studies using different organs of the mice demonstrate that the tumor sites in the breast of the mice are most affected by these formulations. Cytotoxicity assays and cellular uptake studies suggest that the present systems can be used for potential applications for gene delivery and oncological therapies.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"261 ","pages":"Article 113066"},"PeriodicalIF":3.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142663986","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 : 2024-11-12DOI: 10.1016/j.jphotobiol.2024.113064
Rubén Gutiérrez-Fuentes , Libertad Juárez-Santacruz , Issis Claudette Romero-Ibarra , José Luis Jiménez-Pérez , Angel Netzahual-Lopantzi
SiO2@Au nanoshells have gained relevance in recent years, especially in biomedical areas, acting as thermal therapy agents due to their high capacity to absorb light and transform it into heat that increases the temperature of the medium. Therefore, it is important to develop methodological strategies to obtain stable, highly specific and biocompatible nanoparticles. In this work, the synthesis of core-shell structures based on SiO2@Au is reported, where the growth a thin shell ⁓ 46 nm on silica platform was possible. Subsequently, optimal conditions were developed for the binding of a bovine serum albumin (BSA) protein using a thiolated linker such as mercaptoethanol. Likewise, the photothermal conversion capacity was investigated using thermal lens spectroscopy. Thermal diffusivity values were reported for the first time during the conjugation process of gold nanoshells, where an increase of 37.5 % was recorded as the conjugation was completed. Finally, the cytotoxic potential of the developed nanoconjugates was evaluated through their hemolytic rate in human red blood cells. The findings suggest high hemocompatibility of the SiO2@Au-BSA complex because they did not cause significant oxidative stress and are classified as nonhemolytic. Therefore, in this work we propose a synthesis route for a thermal agent based on SiO2@Au and bovine serum albumin, highly biocompatible and with high photothermal conversion. The results of this work aim to clarify the safety of using gold nanoshells as a thermal therapy agent.
{"title":"Fabrication of highly biocompatible SiO2@Au-BSA nanoconjugates: Towards a promising thermal therapy route","authors":"Rubén Gutiérrez-Fuentes , Libertad Juárez-Santacruz , Issis Claudette Romero-Ibarra , José Luis Jiménez-Pérez , Angel Netzahual-Lopantzi","doi":"10.1016/j.jphotobiol.2024.113064","DOIUrl":"10.1016/j.jphotobiol.2024.113064","url":null,"abstract":"<div><div>SiO<sub>2</sub>@Au nanoshells have gained relevance in recent years, especially in biomedical areas, acting as thermal therapy agents due to their high capacity to absorb light and transform it into heat that increases the temperature of the medium. Therefore, it is important to develop methodological strategies to obtain stable, highly specific and biocompatible nanoparticles. In this work, the synthesis of core-shell structures based on SiO<sub>2</sub>@Au is reported, where the growth a thin shell ⁓ 46 nm on silica platform was possible. Subsequently, optimal conditions were developed for the binding of a bovine serum albumin (BSA) protein using a thiolated linker such as mercaptoethanol. Likewise, the photothermal conversion capacity was investigated using thermal lens spectroscopy. Thermal diffusivity values were reported for the first time during the conjugation process of gold nanoshells, where an increase of 37.5 % was recorded as the conjugation was completed. Finally, the cytotoxic potential of the developed nanoconjugates was evaluated through their hemolytic rate in human red blood cells. The findings suggest high hemocompatibility of the SiO<sub>2</sub>@Au-BSA complex because they did not cause significant oxidative stress and are classified as nonhemolytic. Therefore, in this work we propose a synthesis route for a thermal agent based on SiO<sub>2</sub>@Au and bovine serum albumin, highly biocompatible and with high photothermal conversion. The results of this work aim to clarify the safety of using gold nanoshells as a thermal therapy agent.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"261 ","pages":"Article 113064"},"PeriodicalIF":3.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682083","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 : 2024-11-12DOI: 10.1016/j.jphotobiol.2024.113065
Anxo Méndez , Francesca Maisto , Jelena Pavlović , Magdaléna Rusková , Domenico Pangallo , Patricia Sanmartín
Night-time outdoor illumination in combination with natural sunlight can influence the visible phototrophic colonizers (mainly algae) growing on stone facades; however, the effects on the microbiome (invisible to the naked eye) are not clear. The presence of stone-dwelling microbes, such as bacteria, diatoms, fungi, viruses and archaea, drives further biological colonization, which may exacerbate the biodeterioration of substrates. Considering the microbiome is therefore important for conservation of the built heritage. The impact of the following types of lighting on the relative abundance and diversity of the microbiome on granite ashlars was evaluated in a year-long outdoor pilot study: no lighting; lighting with a metal halide lamp (a traditional lighting system currently used to illuminate monuments); and lighting with a novel LED lamp (an environmentally sound prototype lamp with a biostatic effect, halting biological colonization by phototrophs, currently under trial). Culturable fractions of microbiome and whole-genome sequencing by metabarcoding with Oxford Nanopore Sequencing (MinION) was conducted for bacteria and fungi in order to complement both community characterization strategies. In addition, the possible biodeteriorative profiles of the isolated strains, relative to calcium carbonate precipitation/solubilisation and iron oxidation/reduction, were investigated by plate assays. Alpha and beta diversity indexes were also determined, along with the abundance of biocide and antibiotic resistance genes. Culture-dependent microbiological analysis failed to properly show changes in community composition, for which metagenomic approaches like MinION are better suited. Thus, MinION analysis identified shifts in the granite microbiome elicited by ornamental lighting. The novel LED lamp with the biostatic effect on phototrophs caused an increase in the diversity of bacteria and fungi. In this case, the microbiome was more similar to that in the unlit samples. In the samples illuminated by the metal halide lamp, dominance of bacteria was favoured and the presence of fungi was negligible.
夜间室外照明与自然阳光相结合，可影响石材外墙生长的可见光营养定居者（主要是藻类）；但对微生物组（肉眼不可见）的影响尚不清楚。石材微生物（如细菌、硅藻、真菌、病毒和古细菌）的存在会进一步推动生物定殖，这可能会加剧基质的生物劣化。因此，考虑微生物群对保护建筑遗产非常重要。在为期一年的室外试点研究中，我们评估了以下几种照明方式对花岗岩灰岩上微生物群的相对丰度和多样性的影响：无照明；使用金属卤化物灯（目前用于古迹照明的传统照明系统）；使用新型 LED 灯（一种具有生物静电效应的环保型原型灯，可阻止光养菌的生物定殖，目前正在试用中）。为了对这两种群落特征描述策略进行补充，还利用牛津纳米孔测序技术（MinION）对细菌和真菌进行了微生物组可培养部分和全基因组测序。此外，还通过平板试验研究了分离菌株在碳酸钙沉淀/溶解和铁氧化/还原方面可能存在的生物劣化特征。此外，还测定了α和β多样性指数，以及生物杀灭剂和抗生素抗性基因的丰度。依赖培养的微生物学分析无法正确显示群落组成的变化，而 MinION 等元基因组学方法更适合显示群落组成的变化。因此，MinION 分析确定了观赏照明引起的花岗岩微生物群的变化。新型 LED 灯对光养菌的生物静电效应增加了细菌和真菌的多样性。在这种情况下，微生物群与未照明样品中的微生物群更为相似。在使用金属卤化物灯照明的样本中，细菌占优势，真菌的存在则微乎其微。
{"title":"Microbiome shifts elicited by ornamental lighting of granite facades identified by MinION sequencing","authors":"Anxo Méndez , Francesca Maisto , Jelena Pavlović , Magdaléna Rusková , Domenico Pangallo , Patricia Sanmartín","doi":"10.1016/j.jphotobiol.2024.113065","DOIUrl":"10.1016/j.jphotobiol.2024.113065","url":null,"abstract":"<div><div>Night-time outdoor illumination in combination with natural sunlight can influence the visible phototrophic colonizers (mainly algae) growing on stone facades; however, the effects on the microbiome (invisible to the naked eye) are not clear. The presence of stone-dwelling microbes, such as bacteria, diatoms, fungi, viruses and archaea, drives further biological colonization, which may exacerbate the biodeterioration of substrates. Considering the microbiome is therefore important for conservation of the built heritage. The impact of the following types of lighting on the relative abundance and diversity of the microbiome on granite ashlars was evaluated in a year-long outdoor pilot study: no lighting; lighting with a metal halide lamp (a traditional lighting system currently used to illuminate monuments); and lighting with a novel LED lamp (an environmentally sound prototype lamp with a biostatic effect, halting biological colonization by phototrophs, currently under trial). Culturable fractions of microbiome and whole-genome sequencing by metabarcoding with Oxford Nanopore Sequencing (MinION) was conducted for bacteria and fungi in order to complement both community characterization strategies. In addition, the possible biodeteriorative profiles of the isolated strains, relative to calcium carbonate precipitation/solubilisation and iron oxidation/reduction, were investigated by plate assays. Alpha and beta diversity indexes were also determined, along with the abundance of biocide and antibiotic resistance genes. Culture-dependent microbiological analysis failed to properly show changes in community composition, for which metagenomic approaches like MinION are better suited. Thus, MinION analysis identified shifts in the granite microbiome elicited by ornamental lighting. The novel LED lamp with the biostatic effect on phototrophs caused an increase in the diversity of bacteria and fungi. In this case, the microbiome was more similar to that in the unlit samples. In the samples illuminated by the metal halide lamp, dominance of bacteria was favoured and the presence of fungi was negligible.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"261 ","pages":"Article 113065"},"PeriodicalIF":3.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643788","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}
Cyclic electron transport (CET) is a vital alternative route that protects against photodamage and aids in energy production. This process depends on proton gradient regulation 5 (PGR5) and PGRL1-dependent pathways associated with CET. The exact roles of these proteins in photosystem I photochemistry under prolonged high light conditions are not fully understood. Continuous light adaptation hinges on two critical mechanisms: alterations in the proton motive force (pmf) and adjustments in the ratio of proteins activated by high light that dissipate excess light through non-photochemical quenching (NPQ). To explore this, we studied pgrl1 and pgr5 mutants to gauge their roles in balancing photochemistry and photoacclimation. These mutants showed inhibited growth, reduced photosynthetic efficiency, and a lowered pmf, leading to diminished non-photochemical energy quenching (qE) under high light. Prolonged high light exposure slowed down unregulated energy losses Y(NO), and relaxation helped regulate photosynthetic activity by increasing photoinhibitory quenching (qI), thus preventing further damage to the photosystem. The precise balance between the two pmf components, ΔpH and Δψ, is critical for controlling photochemistry and photoacclimation, yet remains elusive. In pgr5 reduced pmf led to an accumulation of cytochrome b6f under high light, and a decrease in the ΔpH component and increased the Δψ component's role in photosynthetic acclimation. Notably, light-harvesting complex stress response protein 3 (LHCSR3) showed decreased expression in pgrl1, whereas pgr5 exhibited no expression of both LHCSR3 and LHCSR1 under high-light conditions. Moreover, continuous increase in PSBS protein accumulation in pgr5 suggests enhanced photoprotection in the absence of LHCSR3 under high light. The study provides significant insights into how CET regulates photoprotective proteins LHCSR and PSBS, influencing Chlamydomonas' survival strategies.
{"title":"The interplay between LHCSR and PSBS proteins provides photoprotection in Chlamydomonas reinhardtii pgr5 mutant under high light","authors":"Ranay Mohan Yadav , Nisha Chouhan , Jerome Xavier Gunasekaran , Sai Kiran Madireddi , Aparna Nerusu , Rajagopal Subramanyam","doi":"10.1016/j.jphotobiol.2024.113060","DOIUrl":"10.1016/j.jphotobiol.2024.113060","url":null,"abstract":"<div><div>Cyclic electron transport (CET) is a vital alternative route that protects against photodamage and aids in energy production. This process depends on proton gradient regulation 5 (PGR5) and PGRL1-dependent pathways associated with CET. The exact roles of these proteins in photosystem I photochemistry under prolonged high light conditions are not fully understood. Continuous light adaptation hinges on two critical mechanisms: alterations in the proton motive force (pmf) and adjustments in the ratio of proteins activated by high light that dissipate excess light through non-photochemical quenching (NPQ). To explore this, we studied <em>pgrl1</em> and <em>pgr5</em> mutants to gauge their roles in balancing photochemistry and photoacclimation. These mutants showed inhibited growth, reduced photosynthetic efficiency, and a lowered pmf, leading to diminished non-photochemical energy quenching (qE) under high light. Prolonged high light exposure slowed down unregulated energy losses Y(NO), and relaxation helped regulate photosynthetic activity by increasing photoinhibitory quenching (qI), thus preventing further damage to the photosystem. The precise balance between the two pmf components, ΔpH and Δψ, is critical for controlling photochemistry and photoacclimation, yet remains elusive. In <em>pgr5</em> reduced pmf led to an accumulation of cytochrome <em>b</em><sub>6</sub><em>f</em> under high light, and a decrease in the ΔpH component and increased the Δψ component's role in photosynthetic acclimation. Notably, light-harvesting complex stress response protein 3 (LHCSR3) showed decreased expression in <em>pgrl1</em>, whereas <em>pgr5</em> exhibited no expression of both LHCSR3 and LHCSR1 under high-light conditions. Moreover, continuous increase in PSBS protein accumulation in <em>pgr5</em> suggests enhanced photoprotection in the absence of LHCSR3 under high light. The study provides significant insights into how CET regulates photoprotective proteins LHCSR and PSBS, influencing Chlamydomonas' survival strategies.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"261 ","pages":"Article 113060"},"PeriodicalIF":3.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639259","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 : 2024-11-06DOI: 10.1016/j.jphotobiol.2024.113061
Guogang Dong , Limin Jia , Shuhua Gao , Monan Lin , Ruilin Wang , Fuyu Yang , Juanjuan Ruan , Yanhong Lv
Objective
Sonodynamic therapy (SDT) is an innovative, non-invasive approach to cancer treatment, by using low-intensity ultrasound to trigger the activation of sonosensitizers localized within cancerous cells. This current study aimed to explore the therapeutic efficacy of a new sonosensitizer, Sinoporphyrin Sodium (DVDMS), under ultrasound irradiation, against oral squamous cell carcinoma (OSCC)-derived SCC-154 cells, both in vitro and in vivo.
Methods
Fluorescence spectra, cytotoxicity assessments, uptake mechanisms, and subcellular distributions of DVDMS within the SCC-154 cell line were detected. Additionally, the study comprehensively assessed the antitumor effect, oxidative stress responses, apoptosis, apoptosis-related proteins, autophagic processes, and ultrastructural changes in SCC-154 cells, both in vitro and in vivo, subsequent to treatment with low-intensity ultrasound (at 1.0 MHz, 1 W/cm2 in vitro and 3 W/cm2 in vivo) in conjunction with DVDMS also being examined.
Results
The findings indicate that SCC-154 cells exhibit heightened sensitivity to DVDMS compared to SAS and HSC-3 cell lines. Within SCC-154 cells, DVDMS primarily localizes within the mitochondria and lysosomes. DVDMS-based SDT significantly increased the intracellular levels of reactive oxygen species (ROS), induced morphological changes such as mitochondrial swelling and formation of autolysosomes, and exhibited a notable dose-dependent reduction in cell viability in vitro. Also, DVDMS-SDT demonstrated significant inhibition of xenograft growth without discernible adverse effects. Mechanistically, DVDMS-SDT upregulated Bax expression while downregulating Bcl-2 expression, which led to the Bax/Bcl-2 ratio and induced autophagy.
Conclusion
DVDMS-SDT triggers mitochondrial-dependent apoptosis in SCC-154 cells, unlike 5-ALA and protoporphyrin IX (PpIX). Also, the combination of DVDMS with ultrasound stimulation induces autophagy, with the onset of autophagic processes preceding apoptosis.
{"title":"In vitro and in vivo investigation of the inhibitory effects of Sinoporphyrin sodium-mediated Sonodynamic therapy on human oral squamous cell carcinoma","authors":"Guogang Dong , Limin Jia , Shuhua Gao , Monan Lin , Ruilin Wang , Fuyu Yang , Juanjuan Ruan , Yanhong Lv","doi":"10.1016/j.jphotobiol.2024.113061","DOIUrl":"10.1016/j.jphotobiol.2024.113061","url":null,"abstract":"<div><h3>Objective</h3><div>Sonodynamic therapy (SDT) is an innovative, non-invasive approach to cancer treatment, by using low-intensity ultrasound to trigger the activation of sonosensitizers localized within cancerous cells. This current study aimed to explore the therapeutic efficacy of a new sonosensitizer, Sinoporphyrin Sodium (DVDMS), under ultrasound irradiation, against oral squamous cell carcinoma (OSCC)-derived SCC-154 cells, both in vitro and in vivo.</div></div><div><h3>Methods</h3><div>Fluorescence spectra, cytotoxicity assessments, uptake mechanisms, and subcellular distributions of DVDMS within the SCC-154 cell line were detected. Additionally, the study comprehensively assessed the antitumor effect, oxidative stress responses, apoptosis, apoptosis-related proteins, autophagic processes, and ultrastructural changes in SCC-154 cells, both in vitro and in vivo, subsequent to treatment with low-intensity ultrasound (at 1.0 MHz, 1 W/cm<sup>2</sup> in vitro and 3 W/cm<sup>2</sup> in vivo) in conjunction with DVDMS also being examined.</div></div><div><h3>Results</h3><div>The findings indicate that SCC-154 cells exhibit heightened sensitivity to DVDMS compared to SAS and HSC-3 cell lines. Within SCC-154 cells, DVDMS primarily localizes within the mitochondria and lysosomes. DVDMS-based SDT significantly increased the intracellular levels of reactive oxygen species (ROS), induced morphological changes such as mitochondrial swelling and formation of autolysosomes, and exhibited a notable dose-dependent reduction in cell viability in vitro. Also, DVDMS-SDT demonstrated significant inhibition of xenograft growth without discernible adverse effects. Mechanistically, DVDMS-SDT upregulated Bax expression while downregulating Bcl-2 expression, which led to the Bax/Bcl-2 ratio and induced autophagy.</div></div><div><h3>Conclusion</h3><div>DVDMS-SDT triggers mitochondrial-dependent apoptosis in SCC-154 cells, unlike 5-ALA and protoporphyrin IX (PpIX). Also, the combination of DVDMS with ultrasound stimulation induces autophagy, with the onset of autophagic processes preceding apoptosis.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"261 ","pages":"Article 113061"},"PeriodicalIF":3.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622039","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 : 2024-11-05DOI: 10.1016/j.jphotobiol.2024.113052
Feng Zhang , Hao Cai , Leichen Wang , Jinjun Shao
Thienoisoindigo (TIIG) has been extensively employed as promising building block of near-infrared (NIR) dyes and organic semiconductor materials. Herein, heavy-atom-free TIIG-based NIR dye TIIGTPA is reported as photosensitizer for combinational photodynamic and photothermal therapy and photoacoustic imaging (PAI). By introducing two methoxy-substituted triphenylamines as the rotors and electron donors at the periphery sites of the electron-deficient TIIG core, dye TIIGTPA featuring Donor-Acceptor-Donor (D-AD) structure is constructed with intensive NIR absorption. Through co-assembly with amphipathic F-127, water-soluble TIIGTPA NPs were prepared with good superoxide anion radical (O2-•) production and high photothermal conversion efficiency (PCE) of 59.0 % under 730 nm photoirradiation. Additionally, the excellent photothermal effect enabled a superior photoacoustic response for tumor blood vessel visualization through PAI. All results indicated the favorable potential of TIIGTPA NPs for PAI-mediated combinational phototherapy.
{"title":"Synthesis of heavy-atom-free thienoisoindigo dye as near-infrared photosensitizer for type I photodynamic therapy and photoacoustic imaging","authors":"Feng Zhang , Hao Cai , Leichen Wang , Jinjun Shao","doi":"10.1016/j.jphotobiol.2024.113052","DOIUrl":"10.1016/j.jphotobiol.2024.113052","url":null,"abstract":"<div><div>Thienoisoindigo (TIIG) has been extensively employed as promising building block of near-infrared (NIR) dyes and organic semiconductor materials. Herein, heavy-atom-free TIIG-based NIR dye TIIGTPA is reported as photosensitizer for combinational photodynamic and photothermal therapy and photoacoustic imaging (PAI). By introducing two methoxy-substituted triphenylamines as the rotors and electron donors at the periphery sites of the electron-deficient TIIG core, dye TIIGTPA featuring Donor-Acceptor-Donor (D-A<img>D) structure is constructed with intensive NIR absorption. Through co-assembly with amphipathic F-127, water-soluble TIIGTPA NPs were prepared with good superoxide anion radical (O<sub>2</sub><sup>-•</sup>) production and high photothermal conversion efficiency (PCE) of 59.0 % under 730 nm photoirradiation. Additionally, the excellent photothermal effect enabled a superior photoacoustic response for tumor blood vessel visualization through PAI. All results indicated the favorable potential of TIIGTPA NPs for PAI-mediated combinational phototherapy.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"261 ","pages":"Article 113052"},"PeriodicalIF":3.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605059","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}
Flammulina filiformis, a representative umbelliferous fungus, has a long stipe and high l-lysine content, thus is widely cultivated and consumed. Currently, there is a lack of theoretical guidance on how to better use light to cultivate edible fungi without photosynthesis such as F. filiformis in industrialized cultivation. Previous studies have found that blue light can affect the yield and l-lysine content of F. filiformis. The primary focus of this work was the phytochrome PHY in the light signaling pathway and its role in F. filiformis production. Unlike plants in which the expression of PHY was activated by only red light, it was found that different visible lights (including red, blue, green, and white light) can stimulate the up-regulation of FfPhy transcript levels. Throughout the developmental stages of F. filiformis, the transcript level of FfPhy was significantly up-regulated during the formation of fruiting body and in the stipe in the elongation stage. Further, FfPhy knockdown strain showed the markedly shorter stipe length than WT, resulting in a significantly reduced yield. RNA-Seq analysis showed that the most genes in MAPK signaling pathway and its downstream regulatory processes, mainly focusing on cell division and cell wall remodeling, were down-regulated after FfPhy knockdown. It suggested that FfPhy regulates the fruiting body elongation through acting on cell division and cell wall remodeling, thereby affecting the morphological development of the stipe rather than the pileus. Interestingly, FfPhy knockdown also inhibits the accumulation of l-lysine content by promoting l-lysine degradation instead of inhibiting l-lysine biosynthesis, indicating that its influence extends to metabolic processes related to l-lysine metabolism. These findings provide new insights into photobiological effect of FfPhy in macrofungus F. filiformis, and have potential guiding significance for cultivation and breeding to increase mushroom yield and l-lysine content.
{"title":"Light and phytochrome PHY control the production of edible fungus Flammulina filiformis by regulating the morphogenesis of fruiting bodies and l-lysine accumulation","authors":"Yizhao Chen , Huimin Ju , Hui Li , Chang Xu , Hui Jia , Lijun Xian , Chengjin Yuan , Zexuan Guo , Xijin Zhang , Yilin Yu , Yongxin Tao","doi":"10.1016/j.jphotobiol.2024.113051","DOIUrl":"10.1016/j.jphotobiol.2024.113051","url":null,"abstract":"<div><div><em>Flammulina filiformis</em>, a representative umbelliferous fungus, has a long stipe and high <span>l</span>-lysine content, thus is widely cultivated and consumed. Currently, there is a lack of theoretical guidance on how to better use light to cultivate edible fungi without photosynthesis such as <em>F. filiformis</em> in industrialized cultivation. Previous studies have found that blue light can affect the yield and <span>l</span>-lysine content of <em>F. filiformis</em>. The primary focus of this work was the phytochrome PHY in the light signaling pathway and its role in <em>F. filiformis</em> production. Unlike plants in which the expression of PHY was activated by only red light, it was found that different visible lights (including red, blue, green, and white light) can stimulate the up-regulation of <em>FfPhy</em> transcript levels. Throughout the developmental stages of <em>F. filiformis</em>, the transcript level of <em>FfPhy</em> was significantly up-regulated during the formation of fruiting body and in the stipe in the elongation stage. Further, <em>FfPhy</em> knockdown strain showed the markedly shorter stipe length than WT, resulting in a significantly reduced yield. RNA-Seq analysis showed that the most genes in MAPK signaling pathway and its downstream regulatory processes, mainly focusing on cell division and cell wall remodeling, were down-regulated after <em>FfPhy</em> knockdown. It suggested that <em>FfPhy</em> regulates the fruiting body elongation through acting on cell division and cell wall remodeling, thereby affecting the morphological development of the stipe rather than the pileus. Interestingly, <em>FfPhy</em> knockdown also inhibits the accumulation of <span>l</span>-lysine content by promoting <span>l</span>-lysine degradation instead of inhibiting <span>l</span>-lysine biosynthesis, indicating that its influence extends to metabolic processes related to <span>l</span>-lysine metabolism. These findings provide new insights into photobiological effect of <em>FfPhy</em> in macrofungus <em>F. filiformis</em>, and have potential guiding significance for cultivation and breeding to increase mushroom yield and <span>l</span>-lysine content.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"261 ","pages":"Article 113051"},"PeriodicalIF":3.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592667","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 : 2024-11-02DOI: 10.1016/j.jphotobiol.2024.113050
Félix L. Figueroa , Pablo Castro-Varela , Julia Vega , Raúl Losantos , Beatriz Peñín , Leonardo López-Cóndor , María Jesús Pacheco , Sofía Latorre Redoli , Manuel Marí-Beffa , Roberto Abdala-Díaz , Diego Sampedro
The combination of environmental stress on the ozone layer, climate change and a greater sun exposure due to outdoor habits has led to an increase in skin cancer cases and other health issues related with UV radiation. Researchers are searching for new alternative UV filters that could protect our skin from the deleterious effects of UV radiation while also presenting low toxicity and biodegradable character (unlike the UV filters currently available in the market). In this work, two compounds inspired in the natural oxo-mycosporine-like amino acids (MAAs) have been synthesized and their antioxidant and photoprotective properties, as well as their in vitro and in vivo toxicity effects were evaluated. Both compounds featured a strong UV-B absorption together with a high antioxidant capacity, close to 50 μmol TE g−1 DW in the ABTS assay. Compound 1 presented an absorption peak at 285–300 nm, whereas compound 2 showed a wider band with a peak around 295–305 nm and two shoulders at 318 and 342 nm. The addition of 5 % of compound 2 to galenic formulas increased the photoprotection, reaching SPF values of 4. Both compounds were stable under UV radiation exposure. Regarding toxicity, the synthetic compounds did not show cytotoxic activity against healthy human cell lines or significant toxicity over zebrafish embryos. Compound 1 showed a complete lack of toxicity over zebrafish, although compound 2 showed slight, not-significant effects on viability, hatching, pericardial stability or body axis formation over 5 mg mL−1. Moreover, compound 1 presented relatively antitumoral activities against HCT-116 cells (selective index:1.49). The relevant antioxidant and photoprotective ability together with the great advantage provided by the reduced toxicity to health cells or zebrafish embryos, make these compounds promising candidates to be exploited as functional ingredients with specific applications in the biotechnological or pharma sector.
{"title":"Novel synthetic UV screen compounds inspired in mycosporine-like amino acids (MAAs): Antioxidant capacity, photoprotective properties and toxicity","authors":"Félix L. Figueroa , Pablo Castro-Varela , Julia Vega , Raúl Losantos , Beatriz Peñín , Leonardo López-Cóndor , María Jesús Pacheco , Sofía Latorre Redoli , Manuel Marí-Beffa , Roberto Abdala-Díaz , Diego Sampedro","doi":"10.1016/j.jphotobiol.2024.113050","DOIUrl":"10.1016/j.jphotobiol.2024.113050","url":null,"abstract":"<div><div>The combination of environmental stress on the ozone layer, climate change and a greater sun exposure due to outdoor habits has led to an increase in skin cancer cases and other health issues related with UV radiation. Researchers are searching for new alternative UV filters that could protect our skin from the deleterious effects of UV radiation while also presenting low toxicity and biodegradable character (unlike the UV filters currently available in the market). In this work, two compounds inspired in the natural oxo-mycosporine-like amino acids (MAAs) have been synthesized and their antioxidant and photoprotective properties, as well as their <em>in vitro</em> and <em>in vivo</em> toxicity effects were evaluated. Both compounds featured a strong UV-B absorption together with a high antioxidant capacity, close to 50 μmol TE g<sup>−1</sup> DW in the ABTS assay. Compound <strong>1</strong> presented an absorption peak at 285–300 nm, whereas compound <strong>2</strong> showed a wider band with a peak around 295–305 nm and two shoulders at 318 and 342 nm. The addition of 5 % of compound <strong>2</strong> to galenic formulas increased the photoprotection, reaching SPF values of 4. Both compounds were stable under UV radiation exposure. Regarding toxicity, the synthetic compounds did not show cytotoxic activity against healthy human cell lines or significant toxicity over zebrafish embryos. Compound <strong>1</strong> showed a complete lack of toxicity over zebrafish, although compound <strong>2</strong> showed slight, not-significant effects on viability, hatching, pericardial stability or body axis formation over 5 mg mL<sup>−1</sup>. Moreover, compound <strong>1</strong> presented relatively antitumoral activities against HCT-116 cells (selective index:1.49). The relevant antioxidant and photoprotective ability together with the great advantage provided by the reduced toxicity to health cells or zebrafish embryos, make these compounds promising candidates to be exploited as functional ingredients with specific applications in the biotechnological or pharma sector.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"261 ","pages":"Article 113050"},"PeriodicalIF":3.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-29DOI: 10.1016/j.jphotobiol.2024.113047
Fang Yang , Song Zhang , Xiao Zhang , Chenchen Xu , Xiaoying Hou , Jinting Shang , Binlian Sun , Xiji Shu , Yuchen Liu , Yixiang Li , Haiping Wang
Pyroptosis is a form of inflammatory cell death that has been demonstrated to trigger anti-tumor immune responses. Photodynamic therapy (PDT) is an innovative non-invasive treatment for tumors that effectively destroys tumor cells and boosts anti-tumor immune response. The ability of PDT to trigger pyroptosis and its mechanism of action are yet uncertain. In this study, we firstly verified that PDT effectively eliminates tumor cells. TEM and Western blot analysis demonstrated that tumor cells underwent pyroptosis following PDT therapy. Lipo-Ce6 mostly accumulates in the mitochondria of 4 T1 cells, and abundant ROS generated during PDT severely damage cell mitochondria, leading to the release of mitochondrial DNA, triggering the inflammasome caspase-1 signaling cascade, and ultimately causing cell pyroptosis, in addition NAC (a scavenger of ROS) and EB (a scavenger of mitochondrial DNA) can effectively prevent cell pyroptosis by PDT, which indicated the key role of ROS in PDT induced pyroptosis. Moreover, we also found PDT tiggered immunogenic cell death (ICD). Fourthermore, PDT can efficiently suppress tumor growth, trigger ICD and induce cell pyroptosis in mice. The introducing of immune checkpoint inhibitor BMS202 significantly boosts the tumor inhibition rate and promotes the infiltration of immune cells into the tumor. The body weight and HE.
staining of normal organs primarily indicated the safety of this combined strategy. Our study demonstrated that PDT induced cell pyroptosis through mitochondrial oxidative damage and PDT induced pyroptosis effectively boost anti-cancer immunity, the combination of PDT and immune checkpoint inhibitor may be a promising clinical tumor treatment approaches.
{"title":"Liposomal chlorin e6-mediated photodynamic therapy induces cell pyroptosis and promotes anti-tumor immune effects in breast cancer","authors":"Fang Yang , Song Zhang , Xiao Zhang , Chenchen Xu , Xiaoying Hou , Jinting Shang , Binlian Sun , Xiji Shu , Yuchen Liu , Yixiang Li , Haiping Wang","doi":"10.1016/j.jphotobiol.2024.113047","DOIUrl":"10.1016/j.jphotobiol.2024.113047","url":null,"abstract":"<div><div>Pyroptosis is a form of inflammatory cell death that has been demonstrated to trigger anti-tumor immune responses. Photodynamic therapy (PDT) is an innovative non-invasive treatment for tumors that effectively destroys tumor cells and boosts anti-tumor immune response. The ability of PDT to trigger pyroptosis and its mechanism of action are yet uncertain. In this study, we firstly verified that PDT effectively eliminates tumor cells. TEM and Western blot analysis demonstrated that tumor cells underwent pyroptosis following PDT therapy. Lipo-Ce6 mostly accumulates in the mitochondria of 4 T1 cells, and abundant ROS generated during PDT severely damage cell mitochondria, leading to the release of mitochondrial DNA, triggering the inflammasome caspase-1 signaling cascade, and ultimately causing cell pyroptosis, in addition NAC (a scavenger of ROS) and EB (a scavenger of mitochondrial DNA) can effectively prevent cell pyroptosis by PDT, which indicated the key role of ROS in PDT induced pyroptosis. Moreover, we also found PDT tiggered immunogenic cell death (ICD). Fourthermore, PDT can efficiently suppress tumor growth, trigger ICD and induce cell pyroptosis in mice. The introducing of immune checkpoint inhibitor BMS202 significantly boosts the tumor inhibition rate and promotes the infiltration of immune cells into the tumor. The body weight and HE.</div><div>staining of normal organs primarily indicated the safety of this combined strategy. Our study demonstrated that PDT induced cell pyroptosis through mitochondrial oxidative damage and PDT induced pyroptosis effectively boost anti-cancer immunity, the combination of PDT and immune checkpoint inhibitor may be a promising clinical tumor treatment approaches.</div></div>","PeriodicalId":16772,"journal":{"name":"Journal of photochemistry and photobiology. B, Biology","volume":"261 ","pages":"Article 113047"},"PeriodicalIF":3.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590708","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号