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Nature Communications Jun 2024The development of Type I photosensitizers (PSs) is of great importance due to the inherent hypoxic intolerance of photodynamic therapy (PDT) in the hypoxic...
The development of Type I photosensitizers (PSs) is of great importance due to the inherent hypoxic intolerance of photodynamic therapy (PDT) in the hypoxic microenvironment. Compared to Type II PSs, Type I PSs are less reported due to the absence of a general molecular design strategy. Herein, we report that the combination of typical Type II PS and natural substrate carvacrol (CA) can significantly facilitate the Type I pathway to efficiently generate superoxide radical (O). Detailed mechanism study suggests that CA is activated into thymoquinone (TQ) by local singlet oxygen generated from the PS upon light irradiation. With TQ as an efficient electron transfer mediator, it promotes the conversion of O to O by PS via electron transfer-based Type I pathway. Notably, three classical Type II PSs are employed to demonstrate the universality of the proposed approach. The Type I PDT against S. aureus has been demonstrated under hypoxic conditions in vitro. Furthermore, this coupled photodynamic agent exhibits significant bactericidal activity with an antibacterial rate of 99.6% for the bacterial-infection female mice in the in vivo experiments. Here, we show a simple, effective, and universal method to endow traditional Type II PSs with hypoxic tolerance.
Topics: Benzoquinones; Photosensitizing Agents; Animals; Mice; Female; Photochemotherapy; Electron Transport; Staphylococcus aureus; Cymenes; Anti-Bacterial Agents; Singlet Oxygen; Superoxides; Staphylococcal Infections; Humans; Light; Mice, Inbred BALB C
PubMed: 38858372
DOI: 10.1038/s41467-024-49311-z -
F1000Research 2024Managing recalcitrant oral lichen planus (OLP) can be challenging. Laser therapy has been suggested as an alternative to corticosteroids for treatment. Photodynamic...
BACKGROUND
Managing recalcitrant oral lichen planus (OLP) can be challenging. Laser therapy has been suggested as an alternative to corticosteroids for treatment. Photodynamic therapy (PDT) is a non-invasive technique that enables the removal of lesions without surgery. Photobiomodulation therapy (PBMT) can promote healing and recovery of the lesions.
CASE PRESENTATION
The objective was to treat unresponsive bilateral OLP of the whole buccal mucosae with a combination of PDT and PBMT.
RESULTS
A 43-year-old Thai male presented with the severe painful reticular type of OLP of bilateral buccal mucosae involving upper and lower vestibular areas. The lesions were not remitted with either prednisolone systemic steroids or fluocinolone topical corticosteroids. After undergoing ten sessions of PDT with 10% 5-Aminolevulinic acid (5-ALA) in the form of thermoplastic gel and a 635 nm diode laser at 100 to 400 mW with an energy density of 20 to 30 J/cm in continuous wave mode, combined with five interim-sessions of PBMT using a 635 nm diode laser at 200 to 300 mW with an energy density of 6 to 10 J/cm in continuous wave, the patient reported relief of burning sensation beside remission of lesions without any complications.
CONCLUSION
The wide-spreading recalcitrant OLP with burning sensation can be managed by combining PDT and PBMT.
Topics: Humans; Male; Adult; Photochemotherapy; Lichen Planus, Oral; Mouth Mucosa; Low-Level Light Therapy; Combined Modality Therapy; Aminolevulinic Acid
PubMed: 38854440
DOI: 10.12688/f1000research.146733.1 -
Turkish Journal of Ophthalmology Jun 2024To investigate the clinical efficacy and safety of the modified Cretan protocol in patients with post-laser in situ keratomileusis ectasia (PLE).
OBJECTIVES
To investigate the clinical efficacy and safety of the modified Cretan protocol in patients with post-laser in situ keratomileusis ectasia (PLE).
MATERIALS AND METHODS
In this retrospective study, 26 eyes of 16 patients with PLE were treated with the modified Cretan protocol (combined transepithelial phototherapeutic keratectomy and accelerated corneal collagen cross-linking). Visual, refractive, tomographic, and aberrometric outcomes and point spread function (PSF) were recorded preoperatively and at 6, 12, and 24 months after treatment.
RESULTS
Both uncorrected and best corrected visual acuity were stable at 24 months postoperatively compared to baseline (from 0.89±0.36 to 0.79±0.33 logarithm of the minimum angle of resolution [LogMAR] and 0.31±0.25 to 0.24±0.19 LogMAR, respectively, p>0.05 for all values). The mean K1, K2, Kmean, thinnest corneal thickness, and spherical aberration at baseline were 45.76±5.75 diopters (D), 48.62±6.17 D, 47.13±5.89 D, 433.16±56.86 μm, and -0.21±0.63 μm respectively. These values were reduced to 42.86±6.34 D, 45.92±6.74 D, 44.21±6.4 D, 391.07±54.76 μm, and -0.51±0.58 μm at 24 months postoperatively (p<0.001, p=0.002, p<0.001, p=0.001, and p=0.02, respectively). The mean spherical equivalent, manifest cylinder, Kmax, central corneal thickness, other corneal aberrations (root mean square, trefoil, coma, quatrefoil, astigmatism), and PSF remained stable (p>0.05 for all variables), while anterior and posterior elevation were significantly improved at 24 months postoperatively (p<0.001 and p=0.02, respectively). No surgical complications occurred during the 24-month follow-up.
CONCLUSION
The modified Cretan protocol is a safe and effective treatment option for PLE patients that provides visual stabilization and significant improvement in topographic parameters during the 24-month follow-up. Further studies are needed to support our results.
Topics: Humans; Retrospective Studies; Keratomileusis, Laser In Situ; Male; Female; Visual Acuity; Adult; Dilatation, Pathologic; Corneal Topography; Refraction, Ocular; Cross-Linking Reagents; Treatment Outcome; Photosensitizing Agents; Young Adult; Collagen; Lasers, Excimer; Follow-Up Studies; Riboflavin; Photochemotherapy; Corneal Diseases; Cornea; Postoperative Complications; Myopia; Ultraviolet Rays
PubMed: 38853628
DOI: 10.4274/tjo.galenos.2024.82342 -
Life Sciences Aug 2024As a precursor of protoporphyrin IX (PpIX), an endogenous pro-apoptotic and fluorescent molecule, 5-Aminolevulinic acid (5-ALA) has gained substantial attention for its... (Review)
Review
As a precursor of protoporphyrin IX (PpIX), an endogenous pro-apoptotic and fluorescent molecule, 5-Aminolevulinic acid (5-ALA) has gained substantial attention for its potential in fluorescence-guided surgery as well as photodynamic therapy (PDT). Moreover, 5-ALA-PDT has been suggested as a promising chemo-radio sensitization therapy for various cancers. However, insufficient 5-ALA-induced PpIX fluorescence and the induction of multiple resistance mechanisms may hinder the 5-ALA-PDT clinical outcome. Reduced efficacy and resistance to 5-ALA-PDT can result from genomic alterations, tumor heterogeneity, hypoxia, activation of pathways related to cell surveillance, production of nitric oxide, and most importantly, deregulated 5-ALA transporter proteins and heme biosynthesis enzymes. Understanding the resistance regulatory mechanisms of 5-ALA-PDT may allow the development of effective personalized cancer therapy. Here, we described the mechanisms underlying resistance to 5-ALA-PTD across various tumor types and explored potential strategies to overcome this resistance. Furthermore, we discussed future approaches that may enhance the efficacy of treatments using 5-ALA-PDT.
Topics: Aminolevulinic Acid; Humans; Photochemotherapy; Drug Resistance, Neoplasm; Neoplasms; Photosensitizing Agents; Animals; Protoporphyrins
PubMed: 38852796
DOI: 10.1016/j.lfs.2024.122808 -
Journal of Controlled Release :... Jul 2024Hypoimmunogenicity and the immunosuppressive microenvironment of ovarian cancer severely restrict the capability of immune-mediated tumor killing. Immunogenic cell death...
Hypoimmunogenicity and the immunosuppressive microenvironment of ovarian cancer severely restrict the capability of immune-mediated tumor killing. Immunogenic cell death (ICD) introduces a theoretical principle for antitumor immunity by increasing antigen exposure and presentation. Despite recent research progress, the currently available ICD inducers are still very limited, and many of them can hardly induce sufficient ICD based on traditional endoplasmic reticulum (ER) stress. Accumulating evidence indicates that inducing mitochondrial stress usually shows a higher efficiency in evoking large-scale ICD than that via ER stress. Inspired by this, herein, a mitochondria-targeted polyprodrug nanoparticle (named Mito-CMPN) serves as a much superior ICD inducer, effectively inducing chemo-photodynamic therapy-caused mitochondrial stress in tumor cells. The rationally designed stimuli-responsive polyprodrugs, which can self-assemble into nanoparticles, were functionalized with rhodamine B for mitochondrial targeting, cisplatin and mitoxantrone (MTO) for synergistic chemo-immunotherapy, and MTO also serves as a photosensitizer for photodynamic immunotherapy. The effectiveness and robustness of Mito-CMPNs in reversing the immunosuppressive microenvironment is verified in both an ovarian cancer subcutaneous model and a high-grade serous ovarian cancer model. Our results support that the induction of abundant ICD by focused mitochondrial stress is a highly effective strategy to improve the therapeutic efficacy of immunosuppressive ovarian cancer.
Topics: Female; Ovarian Neoplasms; Mitochondria; Photochemotherapy; Nanoparticles; Animals; Humans; Cell Line, Tumor; Photosensitizing Agents; Antineoplastic Agents; Prodrugs; Immunogenic Cell Death; Mice, Inbred BALB C; Cisplatin; Immunotherapy; Tumor Microenvironment
PubMed: 38849094
DOI: 10.1016/j.jconrel.2024.06.014 -
International Journal of Pharmaceutics Jun 2024Breast cancer has now replaced lung cancer as the most prevalent malignant tumor worldwide, posing a serious health risk to women. We have recently designed a promising...
Breast cancer has now replaced lung cancer as the most prevalent malignant tumor worldwide, posing a serious health risk to women. We have recently designed a promising option strategy for the treatment of breast cancer. In this work, cyclodextrin metal-organic frameworks with high drug-carrying properties were endo-crosslinked by 3,3'dithiodipropionyl chloride to form cubic phase gel nanoparticles, which were drug-loaded and then coated by MCF-7 cell membranes. After intravenous injection, this multifunctional nanomedicine achieved dramatically homologous targeting co-delivery of honokiol and indocyanine green to the breast tumor. Further, the disulfide bonds in the nanostructures achieved glutathione-responsive drug release, induced tumor cells to produce reactive oxygen species and promoted apoptosis, resulting in tumor necrosis, and at the same time, inhibited Ki67 protein expression, which enhanced photochemotherapy, and resulted in a 94.08 % in vivo tumor suppression rate in transplanted tumor-bearing mice. Thereby, this nanomimetic co-delivery system may have a place in breast cancer therapy due to its simple fabrication process, excellent biocompatibility, efficient targeted delivery of insoluble drugs, and enhanced photochemotherapy.
PubMed: 38848796
DOI: 10.1016/j.ijpharm.2024.124310 -
Journal of Refractive Surgery... May 2024To compare the effects of corneal allogenic intrastromal ring segment (CAIRS) implantation on topographical measurements and visual outcomes of patients with keratoconus... (Comparative Study)
Comparative Study
PURPOSE
To compare the effects of corneal allogenic intrastromal ring segment (CAIRS) implantation on topographical measurements and visual outcomes of patients with keratoconus with and without corneal cross-linking (CXL) prior to the time of implantation.
METHODS
Sixty-seven eyes with corneal allograft intrastromal ring segment implantation (KeraNatural; Lions VisionGift) due to advanced keratoconus were included in the study. Thirty-seven eyes had no CXL and 30 eyes had had CXL before being referred to the authors. The changes in spherical equivalent (SE), uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), steep keratometry (K1), flat keratometry (K2), mean keratometry (Kmean), maximum keratometry (Kmax), and thinnest pachymetry were retrospectively analyzed 6 months after the implantation.
RESULTS
The median age was 29 years in the CXL group and 24.0 years in the non-CXL group ( > .05), respectively. All topographical and visual parameters before implantation were similar in both groups ( > .05 for all parameters). At 6 months, CDVA, K1, and Kmean showed higher improvement in the non-CXL group than the CXL group ( = .030, .018, and .039, respectively).
CONCLUSIONS
CAIRS surgery has a flattening effect on both the corneas with and without CXL. The cornea with prior CXL treatment had less flattening effect due to the stiffening effect of prior CXL. .
Topics: Humans; Keratoconus; Corneal Stroma; Cross-Linking Reagents; Visual Acuity; Adult; Male; Female; Prosthesis Implantation; Photosensitizing Agents; Retrospective Studies; Corneal Topography; Young Adult; Prostheses and Implants; Refraction, Ocular; Collagen; Corneal Pachymetry; Riboflavin; Photochemotherapy; Adolescent; Ultraviolet Rays; Corneal Transplantation; Middle Aged; Corneal Cross-Linking
PubMed: 38848056
DOI: 10.3928/1081597X-20240501-01 -
ACS Applied Materials & Interfaces Jun 2024Multidrug-resistant (MDR) bacteria pose serious threats to public health due to the lack of effective and biocompatible drugs to kill MDR bacteria. Photodynamic...
Multidrug-resistant (MDR) bacteria pose serious threats to public health due to the lack of effective and biocompatible drugs to kill MDR bacteria. Photodynamic antibacterial therapy has been widely studied due to its low induction of resistance. However, photosensitizers that can efficiently generate reactive oxygen species (ROS) through both type I and type II mechanisms and that have the capability of multiple modes of action are rarely reported. Addressing this issue, we developed a near-infrared-emitting triphenylamine indole iodoethane (TTII) and its silver(I) self-assembled (TTIIS) aggregation-induced emission (AIE) photosensitizer for multimode bacterial infection therapy. TTII can efficiently produce both Type I ROS OH and Type II ROS O. Interestingly, the Ag(I)-π interaction contributed in TTIIS efficiency promotion of the generation of O. Moreover, by releasing Ag, TTIIS enabled photodynamic-Ag(I) dual-mode sterilization. As a result, TTIIS achieved an effective enhancement of antibacterial activity, with a 1-2-fold boost against multidrug-resistant (MDR ). Both TTII and TTIIS at a concentration as low as 0.55 μg mL can kill more than 98% of methicillin resistant (MRSA) on MRSA-infected full-thickness defect wounds of a mouse, and both TTII and TTIIS were effective in eliminating the bacteria and promoting wound healing.
Topics: Photosensitizing Agents; Silver; Animals; Drug Resistance, Multiple, Bacterial; Mice; Anti-Bacterial Agents; Escherichia coli; Reactive Oxygen Species; Photochemotherapy; Microbial Sensitivity Tests; Methicillin-Resistant Staphylococcus aureus
PubMed: 38847621
DOI: 10.1021/acsami.4c05202 -
ACS Applied Materials & Interfaces Jun 2024The prevalence of pathogenic bacterial infections with high morbidity and mortality poses a widespread challenge to the healthcare system. Therefore, it is imperative to...
Dual pH- and ATP-Responsive Antibacterial Nanospray: On-Demand Release of Antibacterial Factors, Imaging Monitoring, and Accelerated Healing of Bacteria-Infected Wounds under NIR Activation.
The prevalence of pathogenic bacterial infections with high morbidity and mortality poses a widespread challenge to the healthcare system. Therefore, it is imperative to develop nanoformulations capable of adaptively releasing antimicrobial factors and demonstrating multimodal synergistic antimicrobial activity. Herein, an NIR-activated multifunctional synergistic antimicrobial nanospray MXene/ZIF-90@ICG was prepared by incorporating ZIF-90@ICG nanoparticles onto MXene-NH nanosheets. MXene/ZIF-90@ICG can on-demand release the antimicrobial factors MXenes, ICG, and Zn in response to variations in pH and ATP levels within the bacterial infection microenvironment. Under NIR radiation, the combination of MXenes, Zn, and ICG generated a significant amount of ROS and elevated heat, thereby enhancing the antimicrobial efficacy of PDT and PTT. Meanwhile, NIR excitation could accelerate the further release of ICG and Zn, realizing the multimodal synergistic antibacterial effect of PDT/PTT/Zn. Notably, introducing MXenes improved the dispersion of the synthesized antimicrobial nanoparticles in aqueous solution, rendering MXene/ZIF-90@ICG a candidate for application as a nanospray. Importantly, MXene/ZIF-90@ICG demonstrated antimicrobial activity and accelerated wound healing in the constructed subcutaneous infection model with NIR activation, maintaining a favorable biosafety level. Therefore, MXene/ZIF-90@ICG holds promise as an innovative nanospray for adaptive multimodal synergistic and efficient antibacterial applications with NIR activation.
Topics: Anti-Bacterial Agents; Animals; Wound Healing; Hydrogen-Ion Concentration; Staphylococcus aureus; Infrared Rays; Adenosine Triphosphate; Mice; Indocyanine Green; Nanoparticles; Microbial Sensitivity Tests; Metal-Organic Frameworks; Escherichia coli; Humans; Photochemotherapy
PubMed: 38847598
DOI: 10.1021/acsami.4c03587 -
Photodermatology, Photoimmunology &... Jul 2024Infections are complications in the wound healing process, and their treatment can lead to antibiotic overuse and bacterial resistance. Antimicrobial photodynamic...
BACKGROUND
Infections are complications in the wound healing process, and their treatment can lead to antibiotic overuse and bacterial resistance. Antimicrobial photodynamic therapy (aPDT) is used to treat infectious diseases caused by fungi, viruses, or bacteria. Methylene blue (MB) and its derivatives are commonly used dyes in antimicrobial photodynamic therapy (aPDT-MB).
METHODS
This study is a PRISMA systematic review of animal models used to discuss the usefulness and therapeutic parameters of aPDT-MB or its derivatives for treating infected skin wounds.
RESULTS
After an extensive literature review, 13 controlled trials totaling 261 animals were selected to evaluate skin infection by leishmaniasis and cutaneous bacterial and fungal infections. All studies found results favoring the use of aPDT-MB. Great variability in parameters was found for radiant exposure from 12 to 360 J/cm, MB diluted in saline solution or distilled water, irradiation time from 40 to 3600 s, irradiance most commonly at a maximum of 100 mW/cm, and wavelength used mainly in the 630-670 nm range.
CONCLUSION
MB is a safe and promising agent used as a photosensitizer in aPDT for skin-infected lesions. There is great variability in the parameters found. Comparisons concerning concentration, irradiation time, and light intensity need to be performed.
Topics: Animals; Disease Models, Animal; Methylene Blue; Photochemotherapy; Photosensitizing Agents
PubMed: 38845020
DOI: 10.1111/phpp.12978