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Green Light-Triggered Photocatalytic Anticancer Activity of Terpyridine-Based Ru(II) Photocatalysts.Inorganic Chemistry Apr 2024The relentless increase in drug resistance of platinum-based chemotherapeutics has opened the scope for other new cancer therapies with novel mechanisms of action (MoA)....
The relentless increase in drug resistance of platinum-based chemotherapeutics has opened the scope for other new cancer therapies with novel mechanisms of action (MoA). Recently, photocatalytic cancer therapy, an intrusive catalytic treatment, is receiving significant interest due to its multitargeting cell death mechanism with high selectivity. Here, we report the synthesis and characterization of three photoresponsive Ru(II) complexes, viz., [Ru(ph-tpy)(bpy)Cl]PF (), [Ru(ph-tpy)(phen)Cl]PF (), and [Ru(ph-tpy)(aip)Cl]PF (), where, ph-tpy = 4'-phenyl-2,2':6',2″-terpyridine, bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, and aip = 2-(anthracen-9-yl)-1-imidazo[4,5-][1,10] phenanthroline, showing photocatalytic anticancer activity. The X-ray crystal structures of and revealed a distorted octahedral geometry with a RuNCl core. The complexes showed an intense absorption band in the 440-600 nm range corresponding to the metal-to-ligand charge transfer (MLCT) that was further used to achieve the green light-induced photocatalytic anticancer effect. The mitochondria-targeting photostable complex induced phototoxicity with IC and PI values of ca. 0.7 μM and 88, respectively, under white light irradiation and ca. 1.9 μM and 35 under green light irradiation against HeLa cells. The complexes (-) showed negligible dark cytotoxicity toward normal splenocytes (IC > 50 μM). The cell death mechanistic study revealed that induced ROS-mediated apoptosis in HeLa cells via mitochondrial depolarization under white or green light exposure. Interestingly, also acted as a highly potent catalyst for NADH photo-oxidation under green light. This NADH photo-oxidation process also contributed to the photocytotoxicity of the complexes. Overall, presented multitargeting synergistic type I and type II photochemotherapeutic effects.
Topics: Humans; Antineoplastic Agents; Apoptosis; Catalysis; Cell Proliferation; Cell Survival; Coordination Complexes; Drug Screening Assays, Antitumor; Green Light; HeLa Cells; Light; Molecular Structure; Photochemical Processes; Pyridines; Reactive Oxygen Species; Ruthenium
PubMed: 38578920
DOI: 10.1021/acs.inorgchem.4c00650 -
RSC Chemical Biology Apr 2024Ruthenium(ii) complexes are attracting significant research attention as a promising class of photosensitizers (PSs) in photodynamic therapy (PDT). Having previously...
Ruthenium(ii) complexes are attracting significant research attention as a promising class of photosensitizers (PSs) in photodynamic therapy (PDT). Having previously reported the synthesis of two novel Ru(ii)-polypyridyl-1,8-naphthalimide Tröger's base compounds 1 and 2 with interesting photophysical properties, where the emission from either the Ru(ii) polypyridyl centres or the naphthalimide moieties could be used to monitor binding to nucleic acids, we sought to use these compounds to investigate further and in more detail their biological profiling, which included unravelling their mechanism of cellular uptake, cellular trafficking and cellular responses to photoexcitation. Here we demonstrate that these compounds undergo rapid time dependent uptake in HeLa cells that involved energy dependent, caveolae and lipid raft-dependent mediated endocytosis, as demonstrated by confocal imaging, and transmission and scanning electron microscopy. Following endocytosis, both compounds were shown to localise to mostly lysosomal and Golgi apparatus compartments with some accumulation in mitochondria but no localisation was found to the nucleus. Upon photoactivation, the compounds increased ROS production and induced ROS-dependent apoptotic cell death. The photo-activated compounds subsequently induced DNA damage and altered tubulin, but not actin structures, which was likely to be an indirect effect of ROS production and induced apoptosis. Furthermore, by changing the concentration of the compounds or the laser used to illuminate the cells, the mechanism of cell death could be changed from apoptosis to necrosis. This is the first detailed biological study of Ru(ii)-polypyridyl Tröger's bases and clearly suggests caveolae-dependent endocytosis is responsible for cell uptake - this may also explain the lack of nuclear uptake for these compounds and similar results observed for other Ru(ii)-polypyridyl complexes. These conjugates are potential candidates for further development as PDT agents and may also be useful in mechanistic studies on cell uptake and trafficking.
PubMed: 38576718
DOI: 10.1039/d3cb00206c -
RSC Advances Mar 2024Conventional Au nanomaterial synthesis typically necessitates the involvement of extensive surfactants and reducing agents, leading to a certain amount of chemical waste...
Conventional Au nanomaterial synthesis typically necessitates the involvement of extensive surfactants and reducing agents, leading to a certain amount of chemical waste and biological toxicity. In this study, we innovatively employed ultra-small graphene oxide as a reducing agent and surfactant for the generation of small Au nanoparticles under ultraviolet irradiation (UV) at ambient conditions. After ultra-small GO-Au seeds were successfully synthesized, we fabricated small star-like Au nanoparticles on the surface of GO, in which GO effectively prevented Austar from aggregation. To further use GO-Austar for cancer PTT therapy, through the modification of reduced human serum albumin-folic acid conjugate (rHSA-FA) and loading IR780, the final probe GO-Austar@rHSA-FA@IR780 was prepared. The prepared probe showed excellent biocompatibility and superb phototoxicity towards MGC-803 cells . , the final probe dramatically increased tumor temperature up to 58.6 °C after 5 minutes of irradiation by an 808 nm laser, significantly inhibiting tumor growth and nearly eradicating subcutaneous tumors in mice. This research provides a novel and simple method for the synthesis of GO-Au nanocomposites, showcasing significant potential in biological applications.
PubMed: 38567330
DOI: 10.1039/d4ra00742e -
Rational design of type-I photosensitizer molecules for mitochondrion-targeted photodynamic therapy.Journal of Materials Chemistry. B Apr 2024Photodynamic therapy (PDT) has emerged as a promising approach for tumor treatment. However, traditional type II PDT faces limitations due to its oxygen-dependent...
Photodynamic therapy (PDT) has emerged as a promising approach for tumor treatment. However, traditional type II PDT faces limitations due to its oxygen-dependent nature. Type-I photosensitizers (PSs) exhibit superiority over conventional type-II PSs owing to their diminished oxygen dependence. Nevertheless, designing effective type-I PSs remains a significant challenge. In this work, we provide a novel strategy to tune the PDT mechanism of an excited photosensitizer through aryl substituent engineering. Using S-rhodamine as the base structure, three PSs were synthesized by incorporating phenyl, furyl, or thienyl groups at the meso position. Interestingly, furyl- or thienyl-substituted S-rhodamine are type-I-dominated PSs that produce O˙, while phenyl S-rhodamine results in O˙ and O through type-I and type-II mechanisms, respectively. Experimental analyses and theoretical calculations showed that the introduction of a five-membered heterocycle at the meso position promoted intersystem crossing (ISC) and electron transfer, facilitating the production of O˙. Furthermore, furyl- or thienyl-substituted S-rhodamine exhibited high phototoxicity at ultralow concentrations. Thienyl-substituted S-rhodamine showed promising PDT efficacy against hypoxic solid tumors. This innovative strategy provides an alternative approach to developing new type-I PSs without the necessity for creating entirely new skeletons.
Topics: Humans; Photosensitizing Agents; Mitochondria; Neoplasms; Photochemotherapy; Oxygen; Rhodamines
PubMed: 38563159
DOI: 10.1039/d4tb00099d -
Obesity (Silver Spring, Md.) May 2024This study aimed to investigate the efficacy and safety of repeated photodynamic therapy (PDT) with a chlorin e6 (Ce6)-embedded intragastric satiety-inducing device...
OBJECTIVE
This study aimed to investigate the efficacy and safety of repeated photodynamic therapy (PDT) with a chlorin e6 (Ce6)-embedded intragastric satiety-inducing device (ISD) to maintain therapeutic effects of obesity in a juvenile pig.
METHODS
The Ce6-embedded ISD was fabricated with a dipping method. Twelve pigs were divided into four groups of three and were administered control, single, biweekly, or weekly PDT, respectively. The therapeutic effects were assessed by comparing the results of phototoxicity, endoscopy, fluoroscopy, hormone and weight changes, and histological examination.
RESULTS
The percentage of total body weight gain was significantly suppressed in PDT-treated pigs compared with control pigs (all p < 0.001). This suppression persisted in the repeated PDT groups, but percentage of total body weight gain gradually increased when PDT was stopped. Ghrelin levels in the PDT-treated groups were significantly lower and leptin levels were significantly higher than those in the control group (all p < 0.05). Inflammatory cell infiltration, collagen, TUNEL, and anti-ghrelin-positive deposition in the weekly group were significantly higher than those in the control, single, and biweekly groups (all p < 0.01).
CONCLUSIONS
Repeated and periodic PDT was technically feasible and safe and successfully maintained the therapeutic effects against obesity while eliminating the indwelling time and reducing ISD-related complications in pigs.
PubMed: 38558513
DOI: 10.1002/oby.23958 -
Neurophotonics Apr 2024Optical imaging has accelerated neuroscience in recent years. Genetically encoded fluorescent activity sensors of calcium, neurotransmitters, and voltage are commonly...
SIGNIFICANCE
Optical imaging has accelerated neuroscience in recent years. Genetically encoded fluorescent activity sensors of calcium, neurotransmitters, and voltage are commonly used for optical recording of neuronal activity. However, fluorescence imaging is limited to superficial regions for activity imaging, due to photon scattering and absorbance. Bioluminescence imaging offers a promising alternative for achieving activity imaging in deeper brain regions without hardware implanted within the brain. Bioluminescent reporters can be genetically encoded and produce photons without external excitation. The use of enzymatic photon production also enables prolonged imaging sessions without the risk of photobleaching or phototoxicity, making bioluminescence suitable for non-invasive imaging of deep neuronal populations.
AIM
To facilitate the adoption of bioluminescent activity imaging, we sought to develop a low cost, simple method that simulates conditions to optimize imaging parameters for determining optimal exposure times and optical hardware configurations to determine what frame rates can be captured with an individual lab's imaging hardware with sufficient signal-to-noise ratios without the use of animals prior to starting an experiment.
APPROACH
We developed an assay for modeling optical conditions with a brain tissue phantom paired with engineered cells that produce bioluminescence. We then used this assay to limit-test the detection depth versus maximum frame rate for bioluminescence imaging at experimentally relevant tissue depths using off-the-shelf imaging hardware.
RESULTS
We developed an assay for modeling optical conditions with a brain tissue phantom paired with engineered cells that produce bioluminescence. With this method, we demonstrate an effective means for increasing the utility of bioluminescent tools and lowering the barrier to adoption of bioluminescence activity imaging.
CONCLUSIONS
We demonstrated an improved method for optimizing imaging parameters for activity imaging with bioluminescent sensors.
PubMed: 38550774
DOI: 10.1117/1.NPh.11.2.024206 -
Advanced Biology May 2024Understanding the intricate processes of neuronal growth, degeneration, and neurotoxicity is paramount for unraveling nervous system function and holds significant...
Understanding the intricate processes of neuronal growth, degeneration, and neurotoxicity is paramount for unraveling nervous system function and holds significant promise in improving patient outcomes, especially in the context of chemotherapy-induced peripheral neuropathy (CIPN). These processes are influenced by a broad range of entwined events facilitated by chemical, electrical, and mechanical signals. The progress of each process is inherently linked to phenotypic changes in cells. Currently, the primary means of demonstrating morphological changes rely on measurements of neurite outgrowth and axon length. However, conventional techniques for monitoring these processes often require extensive preparation to enable manual or semi-automated measurements. Here, a label-free and non-invasive approach is employed for monitoring neuronal differentiation and degeneration using quantitative phase imaging (QPI). Operating on unlabeled specimens and offering little to no phototoxicity and photobleaching, QPI delivers quantitative maps of optical path length delays that provide an objective measure of cellular morphology and dynamics. This approach enables the visualization and quantification of axon length and other physical properties of dorsal root ganglion (DRG) neuronal cells, allowing greater understanding of neuronal responses to stimuli simulating CIPN conditions. This research paves new avenues for the development of more effective strategies in the clinical management of neurotoxicity.
Topics: Animals; Ganglia, Spinal; Axons; Cell Differentiation; Neurons; Humans; Mice; Peripheral Nervous System Diseases; Quantitative Phase Imaging
PubMed: 38548657
DOI: 10.1002/adbi.202400020 -
The Science of the Total Environment Jun 2024Perfluoroalkyl substances (PFAS) are of great ecological concern, however, exploration of their impact on bacteria-phytoplankton consortia is limited. This study...
Perfluoroalkyl substances (PFAS) are of great ecological concern, however, exploration of their impact on bacteria-phytoplankton consortia is limited. This study employed a bioassay approach to investigate the effect of unary exposures of increasing concentrations of PFAS (perfluorooctane sulfonate (PFOS) and 6:2 fluorotelomer sulfonate (6:2 FTS)) on microbial communities from the northwestern Gulf of Mexico. Each community was examined for changes in growth and photophysiology, exudate production and shifts in community structure (16S and 18S rRNA genes). 6:2 FTS did not alter the growth or health of phytoplankton communities, as there were no changes relative to the controls (no PFOS added). On the other hand, PFOS elicited significant phototoxicity (p < 0.05), altering PSII antennae size, lowering PSII connectivity, and decreasing photosynthetic efficiency over the incubation (four days). PFOS induced a cellular protective response, indicated by significant increases (p < 0.001) in the release of transparent exopolymer particles (TEP) compared to the control. Eukaryotic communities (18S rRNA gene) changed substantially (p < 0.05) and to a greater extent than prokaryotic communities (16S rRNA gene) in PFOS treatments. Community shifts were concentration-dependent for eukaryotes, with the low treatment (5 mg/L PFOS) dominated by Coscinodiscophyceae (40 %), and the high treatment (30 mg/L PFOS) marked by a Trebouxiophyceae (50 %) dominance. Prokaryotic community shifts were not concentration dependent, as both treatment levels became depleted in Cyanobacteriia and were dominated by members of the Bacteroidia, Gammaproteobacteria, and Alphaproteobacteria classes. Further, PFOS significantly decreased (p < 0.05) the Shannon diversity and Pielou's evenness across treatments for eukaryotes, and in the low treatment (5 mg/L PFOS) for prokaryotes. These findings show that photophysiology was not impacted by 6:2 FTS but PFOS elicited toxicity that impacted photosynthesis, exudate release, and community composition. This research is crucial in understanding how PFOS impacts microbial communities.
Topics: Fluorocarbons; Photosynthesis; Alkanesulfonic Acids; Water Pollutants, Chemical; Phytoplankton; Microbiota; Gulf of Mexico; Bacteria
PubMed: 38547969
DOI: 10.1016/j.scitotenv.2024.171977 -
International Journal of Molecular... Mar 2024Nanoparticles (NPs) represent a potential optoelectronic source capable of significantly boosting hydrogen production; however, their inevitable cytotoxicity may lead to...
Nanoparticles (NPs) represent a potential optoelectronic source capable of significantly boosting hydrogen production; however, their inevitable cytotoxicity may lead to oxidative damage of bacterial cell membranes. In this study, we employed non-photosynthetic K-12 as a model organism and utilized self-assembled cadmium sulfide (CdS) nanoparticles to construct a low-toxicity and hydrogen-production-enhancing self-photosensitive hybrid system. To mitigate the cytotoxicity of CdS NPs and synthesize biocompatible CdS NPs on the cell surface, we employed engineered (/OE) for bioremediation, achieving this goal through the overexpression of the peroxidase enzyme (EfeB). A comparative analysis with -CdS revealed a significant downregulation of genes encoding oxidative stress proteins in /OE-CdS post-irradiation. Atomic force microscopy (AFM) confirmed the stability of bacterial cell membranes. Due to the enhanced stability of the cell membrane, the hydrogen yield of the /OE-CdS system increased by 1.3 times compared to the control, accompanied by a 49.1% reduction in malondialdehyde (MDA) content. This study proposes an effective strategy to alleviate the toxicity of mixed biological nanoparticle systems and efficiently harness optoelectronic electrons, thereby achieving higher hydrogen production in bioremediation.
Topics: Humans; Escherichia coli; Escherichia coli K12; Nanoparticles; Dermatitis, Phototoxic; Sulfides; Hydrogen; Cadmium Compounds
PubMed: 38542058
DOI: 10.3390/ijms25063085 -
Rapid Communications in Mass... May 2024Lomefloxacin hydrochloride ear drops are highly unstable to light and prone to produce photodegradation impurities. These impurities might be related to the...
Study of the impurity profile of photodegradation in lomefloxacin hydrochloride ear drops using liquid chromatography combined with ion trap/time-of-flight mass spectrometry.
RATIONALE
Lomefloxacin hydrochloride ear drops are highly unstable to light and prone to produce photodegradation impurities. These impurities might be related to the phototoxicity of lomefloxacin, which could seriously threaten the health of patients. In this article, the photodegradation impurity profile in lomefloxacin hydrochloride ear drops was studied for further improvement of quality control of the drug.
METHODS
By studying the chromatographic behavior of photodegradation impurities, the photodegradation impurities in lomefloxacin hydrochloride ear drops were separated and detected effectively. Liquid chromatography combined with ion trap/time-of-flight mass spectrometry was applied to characterize the structures of the photodegradation impurities in lomefloxacin hydrochloride ear drops.
RESULTS
The structures of 17 impurities in lomefloxacin hydrochloride ear drops were elucidated based on high-resolution MS data in positive ion mode, 12 of them being unknown impurities.
CONCLUSIONS
The structural characteristics and fragmentation patterns of the photodegradation impurities were also studied. The study of the photodegradation impurity profile in lomefloxacin hydrochloride ear drops provides a scientific basis for quality control of these ear drops and ensures the safety of drug use by the public.
Topics: Humans; Photolysis; Drug Contamination; Chromatography, Liquid; Gas Chromatography-Mass Spectrometry; Chromatography, High Pressure Liquid; Fluoroquinolones
PubMed: 38525499
DOI: 10.1002/rcm.9732