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International Journal of Pharmaceutics Apr 2024Photodynamic therapy (PDT) is a suitable alternative to currently employed cancer treatments. However, the hydrophobicity of most photosensitizers (e.g., zinc...
Photodynamic therapy (PDT) is a suitable alternative to currently employed cancer treatments. However, the hydrophobicity of most photosensitizers (e.g., zinc phthalocyanine (ZnPC)) leads to their aggregation in blood. Moreover, non-specific accumulation in skin and low clearance rate of ZnPC leads to long-lasting skin photosensitization, forcing patients with a short life expectancy to remain indoors. Consequently, the clinical implementation of these photosensitizers is limited. Here, benzyl-poly(ε-caprolactone)-b-poly(ethylene glycol) micelles encapsulating ZnPC (ZnPC-M) were investigated to increase the solubility of ZnPC and its specificity towards cancers cells. Asymmetric flow field-flow fractionation was used to characterize micelles with different ZnPC-to-polymer ratios and their stability in human plasma. The ZnPC-M with the lowest payload (0.2 and 0.4% ZnPC w/w) were the most stable in plasma, exhibiting minimal ZnPC transfer to lipoproteins, and induced the highest phototoxicity in three cancer cell lines. Nanobodies (Nbs) with binding specificity towards hepatocyte growth factor receptor (MET) or epidermal growth factor receptor (EGFR) were conjugated to ZnPC-M to facilitate cell targeting and internalization. MET- and EGFR-targeting micelles enhanced the association and the phototoxicity in cells expressing the target receptor. Altogether, these results indicate that ZnPC-M decorated with Nbs targeting overexpressed proteins on cancer cells may provide a better alternative to currently approved formulations.
Topics: Humans; Photosensitizing Agents; Micelles; Polymers; Photochemotherapy; Zinc Compounds; Organometallic Compounds; ErbB Receptors; Cell Line, Tumor; Isoindoles
PubMed: 38492899
DOI: 10.1016/j.ijpharm.2024.124004 -
Photodiagnosis and Photodynamic Therapy Apr 2024Conventional photodynamic therapy (c-PDT) is an effective treatment for actinic keratoses (AKs) and nonmelanoma skin cancer which exploits the photosensitizing... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Conventional photodynamic therapy (c-PDT) is an effective treatment for actinic keratoses (AKs) and nonmelanoma skin cancer which exploits the photosensitizing properties of methyl aminolaevulinate (MAL). Daylight photodynamic therapy (DL-PDT) is an alternative to c-PDT which does not require the application of MAL in occlusion and that is better tolerated by patients. The impact of occlusion on the efficacy of DL-PD has not been investigated by previous studies.
OBJECTIVE
To compare the efficacy and tolerability of occlusive and non-occlusive DL-PDT.
METHODS
We conducted a prospective intraindividual left/right comparison study. AKs of the face or scalp were marked in two symmetrical treatment areas. The two target areas were randomly assigned to DL-PDT with occlusive and non-occlusive application of MAL. The efficacy and cosmetic outcome were determined by a "blinded" investigator.
RESULTS
Lesions in occluded areas showed a better response in the clearance rate of the lesions (65.5% vs 35.0 %, p < 0.001 %), and cosmetic outcome (P < 0.001). There was no difference in phototoxicity or pain between occluded and non-occluded areas.
CONCLUSION
The occlusive application of MAL improves the efficacy of DL-PDT in clearing AKs and does not increase the incidence of side effects.
Topics: Keratosis, Actinic; Humans; Aminolevulinic Acid; Photochemotherapy; Photosensitizing Agents; Male; Aged; Female; Prospective Studies; Middle Aged; Aged, 80 and over; Treatment Outcome; Sunlight
PubMed: 38490345
DOI: 10.1016/j.pdpdt.2024.104049 -
Frontiers in Physiology 2024Solar radiation can cause damage to the skin, and the use of sunscreens is one of the main protective measures. However, photounstable ultraviolet (UV) filters can...
Solar radiation can cause damage to the skin, and the use of sunscreens is one of the main protective measures. However, photounstable ultraviolet (UV) filters can generate photoproducts and reactive oxygen species (ROS). Adding antioxidants, such as resveratrol, to enhance the action of UV filters in sunscreens is an interesting strategy for reducing the damage caused by UV radiation exposure. However, new compounds must have their stability, safety and efficacy guaranteed. Avobenzone, a commonly used UV filter, stands out as a promising candidate for structural modification to enhance its stability. Its molecular hybridization with other UV filters and antioxidants can lead to safer and more effective compounds. In this study, the photoprotective and antioxidant potential of a derivative of avobenzone, hybridized with resveratrol's molecule, was evaluated using models of cells in monolayer and reconstructed human skin (RHS). Phototoxic potential was assessed using fibroblasts, while the antioxidant activity was measured using the DCFH-DA probe in HaCaT keratinocytes and in-house RHS. The derivative exhibited UV absorption and demonstrated photostability. It did not exhibit any phototoxic nor photoreactivity potential. Additionally, it was able to photo stabilize a combination of photounstable UV filters, avobenzone and octyl methoxycinnamate, and to reduce their phototoxic potential. In terms of antioxidant activity, the derivative successfully protected against UVA-induced ROS production in the HaCaT keratinocytes model, showing statistical equivalence to the antioxidant control, quercetin (10 μg/mL). Furthermore, experiments conducted in the RHS model demonstrated a significant reduction of 30.7% in ROS generation compared to the irradiated control. This study demonstrated that structural modifications of avobenzone can lead to the development of a broad spectrum (absorbing UVB and UVA II radiation, as well as a portion of the UVA I radiation), non-phototoxic, non-photoreactive and photostable derivative for sunscreen and anti-aging formulations. This derivative enhances protection against oxidative stress induced by UV radiation and improves the effectiveness of sun protection. In addition to the monolayer model, the use of a standardized in-house RHS model was highly relevant for evaluating the effects of UV radiation and skin aging. This model closely mimics human physiological conditions and enables the testing of new compounds and the investigation of protective mechanisms against skin damage.
PubMed: 38487263
DOI: 10.3389/fphys.2024.1347414 -
Journal of Biomedical Optics Mar 2024Label-free nonlinear optical microscopy has become a powerful tool for biomedical research. However, the possible photodamage risk hinders further clinical applications.
SIGNIFICANCE
Label-free nonlinear optical microscopy has become a powerful tool for biomedical research. However, the possible photodamage risk hinders further clinical applications.
AIM
To reduce these adverse effects, we constructed a new platform of simultaneous label-free autofluorescence multi-harmonic (SLAM) microscopy, featuring four-channel multimodal imaging, inline photodamage monitoring, and pulse repetition-rate tuning.
APPROACH
Using a large-core birefringent photonic crystal fiber for spectral broadening and a prism compressor for pulse pre-chirping, this system allows users to independently adjust pulse width, repetition rate, and energy, which is useful for optimizing imaging conditions towards no/minimal photodamage.
RESULTS
It demonstrates label-free multichannel imaging at one excitation pulse per image pixel and thus paves the way for improving the imaging speed by a faster optical scanner with a low risk of nonlinear photodamage. Moreover, the system grants users the flexibility to autonomously fine-tune repetition rate, pulse width, and average power, free from interference, ensuring the discovery of optimal imaging conditions with high SNR and minimal phototoxicity across various applications.
CONCLUSIONS
The combination of a stable laser source, independently tunable ultrashort pulse, photodamage monitoring features, and a compact design makes this new system a robust, powerful, and user-friendly imaging platform.
Topics: Lasers; Photons; Nonlinear Optical Microscopy; Microscopy, Fluorescence, Multiphoton
PubMed: 38487259
DOI: 10.1117/1.JBO.29.3.036501 -
Advanced Science (Weinheim,... Jun 2024To accelerate the pace in the field of photothermal therapy (PTT), it is urged to develop easily accessible photothermal agents (PTAs) showing high photothermal...
Easy but Efficient: Facile Approach to Molecule with Theoretically Justified Donor-Acceptor Structure for Effective Photothermal Conversion and Intravenous Photothermal Therapy.
To accelerate the pace in the field of photothermal therapy (PTT), it is urged to develop easily accessible photothermal agents (PTAs) showing high photothermal conversion efficiency (PCE). As a proof-of-concept, hereby a conventional strategy is presented to prepare donor-acceptor (D-A) structured PTAs through cycloaddition-retroelectrocyclization (CA-RE) reaction, and the resultant PTAs give high PCE upon near-infrared (NIR) irradiation. By joint experimental-theoretical study, these PTAs exhibit prominent D-A structure with strong intramolecular charge transfer (ICT) characteristics and significantly twisting between D and A units which account for the high PCEs. Among them, the DMA-TCNQ exhibits the strongest absorption in NIR range as well as the highest PCE of 91.3% upon irradiation by 760-nm LED lamp (1.2 W cm). In vitro and in vivo experimental results revealed that DMA-TCNQ exhibits low dark toxicity and high phototoxicity after IR irradiation along with nude mice tumor inhibition up to 81.0% through intravenous therapy. The findings demonstrate CA-RE reaction as a convenient approach to obtain twisted D-A structured PTAs for effective PTT and probably promote the progress of cancer therapies.
Topics: Animals; Photothermal Therapy; Mice; Mice, Nude; Disease Models, Animal; Humans; Cell Line, Tumor; Infrared Rays; Neoplasms
PubMed: 38477060
DOI: 10.1002/advs.202309068 -
Sensors (Basel, Switzerland) Feb 2024Optical microscopy techniques are among the most used methods in biomedical sample characterization. In their more advanced realization, optical microscopes demonstrate... (Review)
Review
Optical microscopy techniques are among the most used methods in biomedical sample characterization. In their more advanced realization, optical microscopes demonstrate resolution down to the nanometric scale. These methods rely on the use of fluorescent sample labeling in order to break the diffraction limit. However, fluorescent molecules' phototoxicity or photobleaching is not always compatible with the investigated samples. To overcome this limitation, quantitative phase imaging techniques have been proposed. Among these, holographic imaging has demonstrated its ability to image living microscopic samples without staining. However, for a 3D assessment of samples, tomographic acquisitions are needed. Tomographic Diffraction Microscopy (TDM) combines holographic acquisitions with tomographic reconstructions. Relying on a 3D synthetic aperture process, TDM allows for 3D quantitative measurements of the complex refractive index of the investigated sample. Since its initial proposition by Emil Wolf in 1969, the concept of TDM has found a lot of applications and has become one of the hot topics in biomedical imaging. This review focuses on recent achievements in TDM development. Current trends and perspectives of the technique are also discussed.
PubMed: 38475130
DOI: 10.3390/s24051594 -
International Journal of Molecular... Mar 2024-retinylidene--retinylethanolamine (A2E) has been associated with age-related macular degeneration (AMD) physiopathology by inducing cell death, angiogenesis and...
-retinylidene--retinylethanolamine (A2E) has been associated with age-related macular degeneration (AMD) physiopathology by inducing cell death, angiogenesis and inflammation in retinal pigmented epithelial (RPE) cells. It was previously thought that the A2E effects were solely mediated via the retinoic acid receptor (RAR)-α activation. However, this conclusion was based on experiments using the RAR "specific" antagonist RO-41-5253, which was found to also be a ligand and partial agonist of the peroxisome proliferator-activated receptor (PPAR)-γ. Moreover, we previously reported that inhibiting PPAR and retinoid X receptor (RXR) transactivation with norbixin also modulated inflammation and angiogenesis in RPE cells challenged in the presence of A2E. Here, using several RAR inhibitors, we deciphered the respective roles of RAR, PPAR and RXR transactivations in an in vitro model of AMD. We showed that BMS 195614 (a selective RAR-α antagonist) displayed photoprotective properties against toxic blue light exposure in the presence of A2E. BMS 195614 also significantly reduced the AP-1 transactivation and mRNA expression of the inflammatory interleukin (IL)-6 and vascular endothelial growth factor (VEGF) induced by A2E in RPE cells in vitro, suggesting a major role of RAR in these processes. Surprisingly, however, we showed that (1) Norbixin increased the RAR transactivation and (2) AGN 193109 (a high affinity pan-RAR antagonist) and BMS 493 (a pan-RAR inverse agonist), which are photoprotective against toxic blue light exposure in the presence of A2E, also inhibited PPARs transactivation and RXR transactivation, respectively. Therefore, in our in vitro model of AMD, several commercialized RAR inhibitors appear to be non-specific, and we propose that the phototoxicity and expression of IL-6 and VEGF induced by A2E in RPE cells operates through the activation of PPAR or RXR rather than by RAR transactivation.
Topics: Anti-Inflammatory Agents; Carotenoids; Drug Inverse Agonism; Inflammation; Macular Degeneration; para-Aminobenzoates; Peroxisome Proliferator-Activated Receptors; Quinolines; Retinoic Acid Receptor alpha; Retinoid X Receptors; Retinoids; Transcriptional Activation; Vascular Endothelial Growth Factor A
PubMed: 38474284
DOI: 10.3390/ijms25053037 -
European Journal of Pharmaceutical... May 2024Lung cancer is one of the most common causes of high mortality worldwide. Current treatment strategies, e.g., surgery, radiotherapy, chemotherapy, and immunotherapy,...
Lung cancer is one of the most common causes of high mortality worldwide. Current treatment strategies, e.g., surgery, radiotherapy, chemotherapy, and immunotherapy, insufficiently affect the overall outcome. In this study, we used curcumin as a natural photosensitizer in photodynamic therapy and encapsulated it in liposomes consisting of stabilizing tetraether lipids aiming for a pulmonary drug delivery system against lung cancer. The liposomes with either hydrolyzed glycerol-dialkyl-glycerol tetraether (hGDGT) in different ratios or hydrolyzed glycerol-dialkyl-nonitol tetraether (hGDNT) were prepared by dual centrifugation (DC), an innovative method for liposome preparation. The liposomes' physicochemical characteristics before and after nebulization and other nebulization characteristics confirmed their suitability. Morphological characterization using atomic force and transmission electron microscopy showed proper vesicular structures indicative of liposomes. Qualitative and quantitative uptake of the curcumin-loaded liposomes in lung adenocarcinoma (A549) cells was visualized and proven. Phototoxic effects of the liposomes were detected on A549 cells, showing decreased cell viability. The generation of reactive oxygen species required for PDT and disruption of mitochondrial membrane potential were confirmed. Moreover, the chorioallantoic membrane (CAM) model was used to further evaluate biocompatibility and photodynamic efficacy in a 3D cell culture context. Photodynamic efficacy was assessed by PET/CT after nebulization of the liposomes onto the xenografted tumors on the CAM with subsequent irradiation. The physicochemical properties and the efficacy of tetraether lipid liposomes encapsulating curcumin, especially liposomes containing hGDNT, in 2D and 3D cell cultures seem promising for future PDT usage against lung cancer.
PubMed: 38471594
DOI: 10.1016/j.ejps.2024.106748 -
Advanced Science (Weinheim,... May 2024High-resolution spatio-temporal monitoring of the cell membrane lipid order provides visual insights into the complex and sophisticated systems that control cellular...
High-resolution spatio-temporal monitoring of the cell membrane lipid order provides visual insights into the complex and sophisticated systems that control cellular physiological functions. Solvatochromic fluorescent probes are highly promising noninvasive visualization tools for identifying the ordering of the microenvironment of plasma membrane microdomains. However, conventional probes, although capable of structural analysis, lack the necessary long-term photostability required for live imaging at the cellular level. Here, an ultra-high-light-resistant solvatochromic fluorescence probe, 2-N,N-diethylamino-7-(4-methoxycarbonylphenyl)-9,9-dimethylfluorene (FπCM) is reported, which enables live lipid order imaging of cell division. This probe and its derivatives exhibit sufficient fluorescence wavelengths, brightness, polarity responsiveness, low phototoxicity, and remarkable photostability under physiological conditions compared to conventional solvatochromic probes. Therefore, these probes have the potential to overcome the limitations of fluorescence microscopy, particularly those associated with photobleaching. FπCM probes can serve as valuable tools for elucidating mechanisms of cellular processes at the bio-membrane level.
Topics: Fluorescent Dyes; Humans; Microscopy, Fluorescence; Optical Imaging; Cell Membrane
PubMed: 38468355
DOI: 10.1002/advs.202309721 -
Biomaterials Advances May 2024Lung cancer, one of the most common causes of high mortality worldwide, still lacks appropriate and convenient treatment options. Photodynamic therapy (PDT) has shown...
Lung cancer, one of the most common causes of high mortality worldwide, still lacks appropriate and convenient treatment options. Photodynamic therapy (PDT) has shown promising results against cancer, especially in recent years. However, pulmonary drug delivery of the predominantly hydrophobic photosensitizers still represents a significant obstacle. Nebulizing DPPC/Cholesterol liposomes loaded with the photosensitizer curcumin via a vibrating mesh nebulizer might overcome current restrictions. In this study, the liposomes were prepared by conventional thin-film hydration and two other methods based on dual centrifugation. The liposomes' physicochemical properties were determined before and after nebulization, showing that liposomes do not undergo any changes. However, morphological characterization of the differently prepared liposomes revealed structural differences between the methods in terms of lamellarity. Internalization of curcumin in lung adenocarcinoma (A549) cells was visualized and quantified. The generation of reactive oxygen species because of the photoreaction was also proven. The photodynamic efficacy of the liposomal formulations was tested against A549 cells. They revealed different phototoxic responses at different radiant exposures. Furthermore, the photodynamic efficacy was investigated after nebulizing curcumin-loaded liposomes onto xenografted tumors on the CAM, followed by irradiation, and evaluated using positron emission tomography/computed tomography and histological analysis. A decrease in tumor metabolism could be observed. Based on the efficacy of curcumin-loaded liposomes in 2D and 3D models, liposomes, especially with prior film formation, can be considered a promising approach for PDT against lung cancer.
Topics: Humans; Liposomes; Curcumin; Drug Delivery Systems; Nebulizers and Vaporizers; Photosensitizing Agents; Lung Neoplasms
PubMed: 38460353
DOI: 10.1016/j.bioadv.2024.213823