Photochemistry and Photobiology最新文献

The direct introduction of ionic character in azoheteroarenes led to the generation of azopyridinium, azoimidazolium, and azopyrazolium photoswitches, which have previously garnered intriguing application prospects due to their varied Z-E thermal relaxation properties. We leveraged this foundation to design and synthesize three azoisoxazolium-based ionic photoswitches, aiming to expand their application scope and tailor their properties. The investigations on their photoswitching characteristics in different solvents, including water, revealed a solvent-dependent aggregation that competes with isomerization, although their thermal relaxations slow down the aggregation. Also, spectroscopic and dynamic light scattering (DLS) studies showed that the azoisoxazolium ionic photoswitches can exhibit negative photochromism, light-induced disaggregation at low concentrations in one of the derivatives, and significantly fluorescence emission in water. In addition, microscopic studies using scanning electron microscope (SEM), transmission electron microscope (TEM), polarized optical microscope (POM), and confocal microscope revealed the size and structural morphology and mesophase changes of the aggregates. Overall, our comprehensive investigation has positioned azoisoxazolium salts as a new class of ionic photoswitches characterized by several intriguing properties and a pronounced tendency to aggregate.

The use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) for tumor fluorescence imaging and photodynamic therapy (PDT) may be limited by intrinsic PpIX-reducing mechanisms including PpIX bioconversion and efflux transport. The effectiveness of targeting these PpIX-reducing mechanisms was evaluated in glioblastoma cell lines. Although either inhibiting PpIX bioconversion by an iron chelator deferoxamine (DFO) or suppressing PpIX efflux by an ABCG2 transporter inhibitor lapatinib (Lap) significantly increased ALA-PpIX and PDT effect in the A172 cell line with weak ABCG2 activity, DFO in combination with Lap led to significantly greater enhancement effects. However, DFO did not significantly enhance ALA in H4, U-87, and U-118 cell lines with robust ABCG2 activities, whereas Lap showed effective enhancement effects. The combination of DFO and Lap enhanced ALA-induced PpIX and PDT in these three cell lines. Not just increasing ALA-PpIX levels, Lap enhanced PpIX localization in the mitochondria and promoted mitochondria-mediated apoptosis after PDT in the H4 cell line with strong ABCG2 activities. Our results demonstrate that blocking ABCG2-mediated PpIX efflux is critical for the enhancement of ALA and, in tumor cells with ABCG2 activities, inhibiting PpIX bioconversion by DFO needs to be combined with PpIX efflux suppression for effective enhancement of ALA.

In this paper, we investigated the response of the larvae of the sea urchin Centrostephanus rodgersii to unpolarized halogen light, darkness as well as polarized (linear, circular and elliptical) halogen light presented in side view to observation chambers. The larvae exhibited positive phototaxis when exposed to unpolarized, horizontally polarized, elliptically polarized, and circularly polarized light. However, they did not respond to vertically polarized light. In fact, larval swimming behavior after exposure to vertically polarized light was the same as keeping them in the dark. These findings indicate that not only may the larvae of C. rodgersii have photoreceptors capable of detecting light in the visible spectrum but they may also possess the capacity to differentiate between horizontally and vertically polarized light, which might help them navigate. These findings suggest the possibility of aligned photoreceptors in these larvae. In addition, we found that the larvae respond to circularly polarized light. This result is notable as there are few documented cases of circular polarization sensitivity in animals. As they did not appear to have a preference between the left- and right-handed polarizations, one would need to study their photoreceptor cells to determine the mechanism by which they can detect circular polarization. This could pave the way to the development of new polarization detectors based on biological mechanisms.

P-glycoprotein (P-gp, ABCB1)-mediated multidrug resistance (MDR) remains a significant barrier to successful chemotherapy outcomes for cancer patients. While photoactivation of verteporfin (VP), a photosensitizer, has demonstrated success for overcoming MDR through direct protein aggregation upon photoactivation and through adenosine triphosphate (ATP) depletion, the impact of VP's formulation on P-gp function and cellular energetics has not been fully characterized in this context. In this study, we screened four well-established VP formulations-liposomal VP (L-VP), lysophosphatidylcholine-conjugated VP (lysoPC VP), liposomal formulation of lysoPC VP (L-lysoPC VP), and a self-assembled VP nanoaggregate (NanoVP), with a free form of VP as a control-for their ability to inhibit P-gp. Using a combination of in vitro intracellular VP accumulation assays, P-gp substrate retention experiments, and Seahorse-based metabolic profiling, we identified NanoVP as the lead formulation for P-gp modulation in cancer cells. NanoVP effectively depleted ATP in drug-resistant cancer cells, while being recognized as a P-gp substrate. Photodynamic priming with NanoVP at sub-cytotoxic light doses enhanced P-gp substrate retention within the cells without damaging P-gp protein, indicating ATP depletion as the primary mode of functional inhibition. These findings highlighted NanoVP's clinical potential to enhance chemotherapeutic efficacy via photoactivation-based modulation of P-gp's function in multidrug-resistant cancers.

Solar ultraviolet (UV) radiation and atmospheric ozone are critical determinants of ecosystem dynamics and human health. This study aimed to assess the terrestrial profile of solar UV radiation and its genotoxic risk in the South American subtropical region (29° S 53° W). From 2005 to 2021, ground-based physical sensors showed an increase of approximately 50% in UVB (280-315 nm; +0.28 kJ/m² per year), but no significant trend in UVA (315-400 nm). Despite the existence of four defined climatic seasons, simultaneous measurements using UVA, UVB, and DNA-based sensors revealed two distinct UV seasons: a high-UV season encompassing spring and summer, and a low-UV season encompassing winter and autumn. Notably, spring sunlight was found to be as genotoxic as summer sunlight, and even winter and autumn sunlight may pose a genotoxic risk on cloudless days, as indicated by measurements of cyclobutane pyrimidine dimers and oxidized bases. Given the rising UVB levels without an increase in UVA, we investigated satellite-derived ozone data from NASA's ozone monitoring instrument (OMI) and total ozone mapping spectrometer (TOMS) sensors across South America and Antarctica. Overall, analysis from 1979 to 2021 showed negative ozone trends at 2° S 54° W (Santarém), 23° S 46° W (São Paulo), and 29° S 53° W (Santa Maria) even after the onset of the Montreal Protocol, while positive trends were observed at 53° S 70° W (Punta Arenas) and 62° S 58° W (Brazilian Antarctic Station) following the protocol. Strikingly, the UVB and ozone trends observed across seasons suggest that ozone is being transported poleward persistently rather than seasonally, possibly driven by a climate change-induced acceleration of the Brewer-Dobson Circulation. This persistent pattern demonstrates that ozone depletion at low and mid-latitudes is not limited to springtime but persists throughout the year. Our findings indicate that low- and mid-latitudes in South America are experiencing climate changes, stratospheric ozone depletion, and increased UVB incidence, resulting in heightened genotoxic risks, highlighting the urgent need for monitoring and mitigation strategies.

Phototaxis refers to an organism's movement toward a light source, while photophobotaxis involves movement into illuminated regions. Although phototaxis in cyanobacteria has been widely studied, photophobotaxis has been investigated in only a few species. In this study, we examined photophobotaxis of 7 single-celled and 11 filamentous cyanobacterial species, among them 3 Nostocales (filaments with heterocysts) and 5 Oscillatoriales and 1 Desertifiliales member. All single-celled species and all Oscillatoriales/Desertifiliales exhibited photophobotaxis, whereas no evidence of photophobotaxis was found for the Nostocales and two other species. A pilus-free mutant of Synechocystis sp. PCC 6803 did not display this behavior. The photosystem II inhibitor DCMU disrupted photophobotaxis in single-celled and filamentous cyanobacteria at a concentration of 10 μM; only the filamentous Phormidium lacuna (P. lacuna) required 100 μM DCMU for inhibition. This points to PS II as a sensor of photophobotaxis. The widespread occurrence of photophobotaxis aligns with the universality of photosystems. Previous studies on spectral sensitivity and the cyanobacteriochrome PixJ in P. lacuna identified PixJ as a negative regulator of photophobotaxis. In pixJ mutants, light sensitivity was increased compared with the wild-type. Dual-wavelength experiments confirmed that yellow light induces PixJ to downregulate photophobotaxis. Our experiments also show that P. lacuna moves faster in darkness than in light and that a temporal change of light intensity from light to dark can induce a change of movement direction. Both findings support the light trap model which is based on random movement and a change of movement direction at the light-dark border.

Cyclobutane pyrimidine dimers (CPDs) are the major photoproducts of DNA produced by direct absorption of UV light but can also be produced indirectly by photosensitization and chemiexcitation. Deamination of C-containing CPDs is responsible for the majority of C to T mutations caused by UV, which have been linked to skin cancer. Another frequent mutagenic photoproduct of DNA is the (6-4) photoproduct (64PP). Because of their roles in causing mutations, NextGen sequencing methods have been developed to determine the location and frequency of these photoproducts in chromosomal DNA. All these methods, however, rely on enzyme-coupled methods that can only detect one photoproduct at a time. There is evidence, however, that the 64PP and certain oxidized bases can photosensitize CPD formation to produce compound lesions. We propose that such rare but possibly important compound lesions can be detected by single-molecule sequencing using nanopores. Herein, we show that site-specific TT CPD and 64PP photoproducts cause a large current drop when sequenced by an Oxford Nanotechnologies R10-based sequencing device. Furthermore, we demonstrate that both single and multiple photoproducts can be detected in UVB-irradiated DNA substrates containing T₁₁- and (PuTT)₄Pu-tracts. We also provide a simple 9mer kmer model that can simulate the nanopore current data.

Photodynamic therapy (PDT) is a photochemistry-based treatment modality that synergizes with traditional agents and can overcome chemoresistance. Eighty percent of ovarian cancer patients develop chemoresistant disease, highlighting the need to identify sources of treatment failure and develop rational combinations. Studies have shown that perfluoroalkyl substances (PFAS) induce chemoresistance in a duration-dependent manner in OVCAR-3 cells. PFAS are widespread drinking water contaminants present in the blood of nearly all Americans. The present study evaluated the ability of photodynamic priming (PDP), a sub-cytotoxic variant of PDT, in combination with chemotherapy to overcome chemoresistance in two OVCAR-3 cell cohorts: PFAS chronically-exposed and outgrown (allowed to "recover" from chronic PFAS exposure). Effectiveness of benzoporphyrin derivative- (BPD-) or aminolevulinic acid-induced protoporphyrin IX-PDP (ALA-PpIX-PDP) was assessed in combination with carboplatin and doxorubicin. In PFAS chronically-exposed cells, BPD-PDP + carboplatin reduced survival fraction compared to carboplatin alone. Mitochondrial membrane potential also decreased significantly in both cohorts following ALA-PpIX-PDP-based combinations. PDP + doxorubicin also successfully overcame chemoresistance arising from chronic PFAS exposure but was less effective than PDP + carboplatin. Together, these findings demonstrate the efficacy of PDP-based combinations in overcoming chronic PFAS exposure-induced chemoresistance and should be explored in pre-clinical models of ovarian cancer.

Interrelated secondary events occur within days and weeks following a spinal cord injury (SCI), constituting a major hurdle in providing both an effective and affordable treatment for spinal cord repair in that it requires a multifaceted approach. Photobiomodulation (PBM) therapy in the red/near-infrared spectrum holds promising reparative potential; however, there are no consistent or defined parameters for PBM delivery, which may explain the limited number of ongoing clinical trials and less-than-optimal reported outcomes. This review outlines the associated complexities of the secondary cascade after SCI, with insights on how and when red/near-infrared irradiation may alleviate these issues. The primary focus is to discuss limitations within the field that may be inhibiting our ability to characterize optimal guidelines and specifications. Ultimately, this review provides a call for action, as there is an urgent need for consensus and standardization of therapeutic preclinical methodologies if we hope to develop treatment protocols that provide a first-line minimally invasive therapy to (i) minimize injury sequelae and (ii) facilitate spinal cord repair. We recommend establishing a universal method to measure the therapeutic dose of light delivered to an injury site and employing standardized methodologies across all studies to assess the benefits of PBM therapy.

Skin photosensitization is a common challenge following intravenous administration of many photodynamic therapy (PDT) drugs, typically lasting days, weeks, or months in laboratory animals and patients. Symptoms of photosensitivity manifest as erythema and edema on skin exposed to sunlight or bright artificial lighting. Recent efforts using nanocarriers to increase photosensitizer accumulation in tumors have also been shown to reduce skin photosensitivity. We previously developed phototheranostic PORPHYSOME (PS) nanoparticles self-assembled from porphyrin-lipid conjugates and capable of potent anti-tumor PDT. Here, we demonstrate in a nonpigmented rat skin model that PS exhibit less severe and shorter-lasting skin photosensitivity compared with an equivalent drug dose of porfimer sodium (PHO), the canonical first-generation PDT drug. At 2, 4, 8, and 12 days post intravenous injection, depilated skin was exposed to escalating doses of simulated solar light. Light exposure 4 days post-injection showed markedly reduced symptoms of skin photosensitivity with PS than PHO. By Day 8, the minimal dose of light eliciting any kind of skin reaction was significantly higher with PS than PHO, and by Day 12, there was no detectable skin response with PS. These differences were attributed to altered intradermal distribution and faster clearance of PS vs. PHO in rat skin.