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Cureus Apr 2024Pseudoporphyria is an uncommon dermatosis resembling porphyria cutanea tarda (PCT). The exclusion of true porphyria, especially PCT, is critically essential for...
Pseudoporphyria is an uncommon dermatosis resembling porphyria cutanea tarda (PCT). The exclusion of true porphyria, especially PCT, is critically essential for diagnosing pseudoporphyria. It has an unknown underlying pathophysiology with a normal or near-normal porphyrin profile. Pseudoporphyria has been associated with chronic renal failure and hemodialysis, medications, and tanning beds. In drug-induced pseudoporphyria cases, eliminating the suspected photosensitizing drug improves the disease typically within weeks to months (on average eight weeks). In genetically predisposed individuals, phototoxic metabolites may trigger the development of skin fragility, bullae, milia, and scarring on the dorsum of the hands and other sun-exposed areas. Wearing a broad-spectrum sunscreen and maintaining strict ultraviolet protection is essential in cases of pseudoporphyria. We report the case of a 20-year-old male who presented to us with complaints of photosensitivity and multiple erosions with irregular scars over photo-exposed areas involving the dorsum of the hands and face predominantly. The patient was evaluated further to determine the underlying cause. A wood's lamp examination of the urine was done, which did not show fluorescence. Based on clinical and laboratory findings, the diagnosis of pseudoporphyria was made, and the patient was started on the oral antimalarial agent hydroxychloroquine sulfate with strict sun protection.
PubMed: 38707054
DOI: 10.7759/cureus.57574 -
Journal of the American Chemical Society Jul 2023To investigate the potential of tumor-targeting photoactivated chemotherapy, a chiral ruthenium-based anticancer warhead, Λ/Δ-[Ru(Phphen)(OH)], was conjugated to the...
To investigate the potential of tumor-targeting photoactivated chemotherapy, a chiral ruthenium-based anticancer warhead, Λ/Δ-[Ru(Phphen)(OH)], was conjugated to the RGD-containing Ac-MRGDH-NH peptide by direct coordination of the M and H residues to the metal. This design afforded two diastereoisomers of a cyclic metallopeptide, Λ-[]Cl and Δ-[]Cl. In the dark, the ruthenium-chelating peptide had a triple action. First, it prevented other biomolecules from coordinating with the metal center. Second, its hydrophilicity made []Cl amphiphilic so that it self-assembled in culture medium into nanoparticles. Third, it acted as a tumor-targeting motif by strongly binding to the integrin ( = 0.061 μM for the binding of Λ-[]Cl to αβ), which resulted in the receptor-mediated uptake of the conjugate . Phototoxicity studies in two-dimensional (2D) monolayers of A549, U87MG, and PC-3 human cancer cell lines and U87MG three-dimensional (3D) tumor spheroids showed that the two isomers of []Cl were strongly phototoxic, with photoindexes up to 17. Mechanistic studies indicated that such phototoxicity was due to a combination of photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) effects, resulting from both reactive oxygen species generation and peptide photosubstitution. Finally, studies in a subcutaneous U87MG glioblastoma mice model showed that []Cl efficiently accumulated in the tumor 12 h after injection, where green light irradiation generated a stronger tumoricidal effect than a nontargeted analogue ruthenium complex []Cl. Considering the absence of systemic toxicity for the treated mice, these results demonstrate the high potential of light-sensitive integrin-targeted ruthenium-based anticancer compounds for the treatment of brain cancer .
Topics: Animals; Humans; Mice; Ruthenium; Prodrugs; Integrins; Peptides, Cyclic; Peptides; Brain Neoplasms; Cell Line, Tumor; Coordination Complexes; Antineoplastic Agents
PubMed: 37379365
DOI: 10.1021/jacs.3c04855 -
Nature Methods Dec 2023Brillouin microscopy is an emerging optical elastography technique capable of assessing mechanical properties of biological samples in a three-dimensional, all-optical...
Brillouin microscopy is an emerging optical elastography technique capable of assessing mechanical properties of biological samples in a three-dimensional, all-optical and noncontact fashion. The typically weak Brillouin scattering signal can be substantially enhanced via a stimulated Brillouin scattering (SBS) process; however, current implementations require high pump powers, which prohibit applications to photosensitive or live imaging of biological samples. Here we present a pulsed SBS scheme that takes advantage of the nonlinearity of the pump-probe interaction. In particular, we show that the required pump laser power can be decreased ~20-fold without affecting the signal levels or spectral precision. We demonstrate the low phototoxicity and high specificity of our pulsed SBS approach by imaging, with subcellular detail, sensitive single cells, zebrafish larvae, mouse embryos and adult Caenorhabditis elegans. Furthermore, our method permits observing the mechanics of organoids and C. elegans embryos over time, opening up further possibilities for the field of mechanobiology.
Topics: Animals; Mice; Microscopy; Caenorhabditis elegans; Zebrafish; Light; Lasers
PubMed: 37884795
DOI: 10.1038/s41592-023-02054-z -
Planta Medica May 2024Photodynamic therapy is a noninvasive cancer treatment that utilizes photosensitizers to generate reactive oxygen species upon light exposure, leading to tumor cell... (Review)
Review
Photodynamic therapy is a noninvasive cancer treatment that utilizes photosensitizers to generate reactive oxygen species upon light exposure, leading to tumor cell apoptosis. Although photosensitizers have shown efficacy in clinical practice, they are associated with certain disadvantages, such as a certain degree of toxicity and limited availability. Recent studies have shown that natural product photosensitizers offer promising options due to their low toxicity and potential therapeutic effects. In this review, we provide a summary and evaluation of the current clinical photosensitizers that are commonly used and delve into the anticancer potential of natural product photosensitizers like psoralens, quinonoids, chlorophyll derivatives, curcumin, chrysophanol, doxorubicin, tetracyclines, Leguminosae extracts, and extract. The emphasis is on their phototoxicity, pharmacological benefits, and effectiveness against different types of diseases. Novel and more effective natural product photosensitizers for future clinical application are yet to be explored in further research. In conclusion, natural product photosensitizers have potential in photodynamic therapy and represent a promising area of research for cancer treatment.
Topics: Photosensitizing Agents; Biological Products; Photochemotherapy; Reactive Oxygen Species; Curcumin; Neoplasms
PubMed: 38423033
DOI: 10.1055/a-2257-9194 -
RSC Advances Jul 2023Fluorophores that emit light in the near infrared (NIR) are advantageous in photonics and imaging due to minimal light scattering, absorption, phototoxicity and...
Fluorophores that emit light in the near infrared (NIR) are advantageous in photonics and imaging due to minimal light scattering, absorption, phototoxicity and autofluorescence in this spectral region. The layered silicate Egyptian blue (CaCuSiO) emits as a bulk material bright and stable fluorescence in the NIR and is a promising NIR fluorescent material for (bio)photonics. Here, we demonstrate a surfactant-based (mild) exfoliation procedure to produce nanosheets (EB-NS) of high monodispersity, heights down to 1 nm and diameters <20 nm in large quantities. The approach combines planetary ball milling, surfactant assisted bath sonication and centrifugation steps. It avoids the impurities that are typical for the harsh conditions of tip-sonication. Several solvents and surfactants were tested and we found the highest yield for sodium dodecyl benzyl sulfate (SDBS) and water. The NIR fluorescence emission ( ≈ 930-940 nm) is not affected by this procedure, is extremely stable and is not affected by quenchers. This enables the use of EB-NS for macroscopic patterning/barcoding of materials in the NIR. In summary, we present a simple and mild route to NIR fluorescent nanosheets that promise high potential as NIR fluorophores for optical applications.
PubMed: 37441047
DOI: 10.1039/d3ra04083f -
Nature Communications Dec 2023Prodrug photolysis enables spatiotemporal control of drug release at the desired lesions. For photoactivated therapy, near-infrared (NIR) light is preferable due to its...
Prodrug photolysis enables spatiotemporal control of drug release at the desired lesions. For photoactivated therapy, near-infrared (NIR) light is preferable due to its deep tissue penetration and low phototoxicity. However, most of the photocleavable groups cannot be directly activated by NIR light. Here, we report a upconversion-like process via only one step of energy transfer for NIR light-triggered prodrug photolysis. We utilize a photosensitizer (PS) that can be activated via singlet-triplet (S-T) absorption and achieve photolysis of boron-dipyrromethene (BODIPY)-based prodrugs via triplet-triplet energy transfer. Using the strategy, NIR light can achieve green light-responsive photolysis with a single-photon process. A wide range of drugs and bioactive molecules are designed and demonstrated to be released under low-irradiance NIR light (100 mW/cm, 5 min) with high yields (up to 87%). Moreover, a micellar nanosystem encapsulating both PS and prodrug is developed to demonstrate the practicality of our strategy in normoxia aqueous environment for cancer therapy. This study may advance the development of photocleavable prodrugs and photoresponsive drug delivery systems for photo-activated therapy.
Topics: Prodrugs; Photolysis; Drug Delivery Systems; Photosensitizing Agents; Energy Transfer
PubMed: 38062051
DOI: 10.1038/s41467-023-43805-y -
Biochimica Et Biophysica Acta.... Aug 2023Over the last years, there is accumulating evidence that acidic organelles can accumulate and release Ca upon cell activation. Hence, reliable recording of Ca dynamics... (Review)
Review
Over the last years, there is accumulating evidence that acidic organelles can accumulate and release Ca upon cell activation. Hence, reliable recording of Ca dynamics in these compartments is essential for understanding the physiopathological aspects of acidic organelles. Genetically encoded Ca indicators (GECIs) are valuable tools to monitor Ca in specific locations, although their use in acidic compartments is challenging due to the pH sensitivity of most available fluorescent GECIs. By contrast, bioluminescent GECIs have a combination of features (marginal pH sensitivity, low background, no phototoxicity, no photobleaching, high dynamic range and tunable affinity) that render them advantageous to achieve an enhanced signal-to-noise ratio in acidic compartments. This article reviews the use of bioluminescent aequorin-based GECIs targeted to acidic compartments. A need for more measurements in highly acidic compartments is identified.
Topics: Aequorin; Calcium; Organelles
PubMed: 37142127
DOI: 10.1016/j.bbamcr.2023.119481 -
BioRxiv : the Preprint Server For... Oct 2023Sample health is critical for live-cell fluorescence microscopy and has promoted light-sheet microscopy that restricts its ultraviolet-visible excitation to one plane...
Sample health is critical for live-cell fluorescence microscopy and has promoted light-sheet microscopy that restricts its ultraviolet-visible excitation to one plane inside a three-dimensional sample. It is thus intriguing that laser-scanning nonlinear optical microscopy, which similarly restricts its near-infrared excitation, has not broadly enabled gentle label-free molecular imaging. We hypothesize that intense near-infrared excitation induces phototoxicity via linear absorption of intrinsic biomolecules with subsequent triplet buildup, rather than the commonly assumed mechanism of nonlinear absorption. Using a reproducible phototoxicity assay based on the time-lapse elevation of auto-fluorescence (hyper-fluorescence) from a homogeneous tissue model (chicken breast), we provide strong evidence supporting this hypothesis. Our study justifies a simple imaging technique, e.g., rapidly scanned sub-80-fs excitation with full triplet-relaxation, to mitigate this ubiquitous linear-absorption-mediated phototoxicity independent of sample types. The corresponding label-free imaging can track freely moving in real-time at an irradiance up to one-half of water optical breakdown.
PubMed: 37873348
DOI: 10.1101/2023.10.09.561579 -
ACS Omega Sep 2023We have designed and synthesized two Ir(III) complexes ( and ) coordinated with an 8-sulfonamidoquinoline derivative ligand as photosensitizers, which exhibit strong red...
We have designed and synthesized two Ir(III) complexes ( and ) coordinated with an 8-sulfonamidoquinoline derivative ligand as photosensitizers, which exhibit strong red phosphorescence emission and a long phosphorescence lifetime. The Ir(III) complexes exhibit a high population of triplet states, which enable red phosphorescence and efficient singlet oxygen generation. and rapidly enter the cancer cells and accumulate in lysosomes, producing large amounts of intracellular singlet oxygen when exposed to light irradiation, eventually leading to cancer cell death, and the phototoxic indexes of complexes and against cancer cells are in the range of 76-228. Overall, our studies indicate that the synthesized Ir(III) complexes with quinoline ligands exhibit photosensitizing properties, effectively inducing cancer cell death when exposed to light. These promising results suggest their potential application in photodynamic therapy.
PubMed: 37779987
DOI: 10.1021/acsomega.3c03234 -
Frontiers in Physiology 2023Aging results in a decline of cellular proteostasis capacity which culminates in the accumulation of phototoxic material, causing the onset of age-related maladies and... (Review)
Review
Aging results in a decline of cellular proteostasis capacity which culminates in the accumulation of phototoxic material, causing the onset of age-related maladies and ultimately cell death. Mechanisms that regulate proteostasis such as cellular stress response pathways sense disturbances in the proteome. They are activated to increase the expression of protein quality control components that counteract cellular damage. Utilizing invertebrate model organisms such as , it has become increasingly evident that the regulation of proteostasis and the activation of cellular stress responses is not a cell autonomous process. In animals, stress responses are orchestrated by signals coming from other tissues, including the nervous system, the intestine and the germline that have a profound impact on determining the aging process. Genetic pathways discovered in that facilitate cell nonautonomous regulation of stress responses are providing an exciting feeding ground for new interventions. In this review I will discuss cell nonautonomous proteostasis mechanisms and their impact on aging as well as ongoing research and clinical trials that can increase organismal proteostasis to lengthen health- and lifespan.
PubMed: 37469564
DOI: 10.3389/fphys.2023.1228490