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International Journal of Nanomedicine 2024Owing to its noninvasive nature, broad-spectrum effectiveness, minimal bacterial resistance, and high efficiency, phototherapy has significant potential for...
PURPOSE
Owing to its noninvasive nature, broad-spectrum effectiveness, minimal bacterial resistance, and high efficiency, phototherapy has significant potential for antibiotic-free antibacterial interventions and combating antibacterial biofilms. However, finding effective strategies to mitigate the detrimental effects of excessive temperature and elevated concentrations of reactive oxygen species (ROS) remains a pressing issue that requires immediate attention.
METHODS
In this study, we designed a pH-responsive cationic polymer sodium nitroside dihydrate/branched polyethylenimine-indocyanine green@polyethylene glycol (SNP/PEI-ICG@PEG) nanoplatform using the electrostatic adsorption method and Schiff's base reaction. Relevant testing techniques were applied to characterize and analyze SNP/PEI-ICG@PEG, proving the successful synthesis of the nanomaterials. In vivo and in vitro experiments were performed to evaluate the antimicrobial properties of SNP/PEI-ICG@PEG.
RESULTS
The morphology and particle size of SNP/PEI-ICG@PEG were observed via TEM. The zeta potential and UV-visible (UV-vis) results indicated the synthesis of the nanomaterials. The negligible cytotoxicity of up to 1 mg/mL of SNP/PEI-ICG@PEG in the presence or absence of light demonstrated its biosafety. Systematic in vivo and in vitro antimicrobial assays confirmed that SNP/PEI-ICG@PEG had good water solubility and biosafety and could be activated by near-infrared (NIR) light and synergistically treated using four therapeutic modes, photodynamic therapy (PDT), gaseous therapy (GT), mild photothermal therapy (PTT, 46 °C), and cation. Ultimately, the development of Gram-positive (G) Staphylococcus aureus () and Gram-negative (G) Escherichia coli () were both completely killed in the free state, and the biofilm that had formed was eliminated.
CONCLUSION
SNP/PEI-ICG@PEG demonstrated remarkable efficacy in achieving controlled multimodal synergistic antibacterial activity and biofilm infection treatment. The nanoplatform thus holds promise for future clinical applications.
Topics: Biofilms; Photochemotherapy; Animals; Polyethylene Glycols; Indocyanine Green; Photothermal Therapy; Infrared Rays; Mice; Staphylococcus aureus; Polyethyleneimine; Escherichia coli; Nitric Oxide; Anti-Bacterial Agents; Humans; Reactive Oxygen Species; Nanoparticles; Particle Size
PubMed: 38882537
DOI: 10.2147/IJN.S454762 -
Photodermatology, Photoimmunology &... Jul 2024Phototherapy has emerged as a safe yet effective form of treatment of atopic dermatitis (AD). Few studies have been done to evaluate the efficacy of phototherapy in...
BACKGROUND/PURPOSE
Phototherapy has emerged as a safe yet effective form of treatment of atopic dermatitis (AD). Few studies have been done to evaluate the efficacy of phototherapy in Asian children. The aim of this study was to review the phototherapy experience in a cohort of Asian pediatric patients with AD at a tertiary dermatologic center in Singapore.
METHODS
A retrospective study of patients 18 years and below with AD who had undergone phototherapy at KK Women's and Children's Hospital, Singapore, over a 4-year period was performed.
RESULTS
Sixty-two patients were identified, between ages 4 and 16 years (mean age 11 years) at the time of commencement of phototherapy. Thirty-five (60%) patients were males and 23 (40%) were females. Most patients had moderate to severe disease, with 60.3% of the patients with an initial body surface area (BSA) involvement of 31%-60% and 13.8% of the patients with an initial BSA involvement of 61%-90%. For patients who had undergone narrowband ultraviolet B (NBUVB) and combined ultraviolet A (UVA) and NBUVB phototherapy, the mean reduction of the Eczema Area and Severity Index (EASI) scores were 11.4 and 7.9, respectively. Common side effects experienced include xerosis, pruritus, erythema, and pain. Other reasons for cessation of therapy in the NBUVB group included time commitment difficulty (9.3%), hyperactivity (2.3%), and claustrophobia (2.3%). Two patients that had photochemotherapy (psoralen + UVA) [PUVA] suffered from post-UVA burns requiring cessation of treatment. More than half of the patients (56.9%) treated with phototherapy experienced treatment success with improvement in Investigator Global Assessment and EASI scores. 86.2% of the patients had good compliance to the treatment regime, 12% had poor-compliance, and 3.4% were lost to follow-up.
CONCLUSION
Phototherapy is a useful treatment adjunct for moderate to severe AD in Asian children.
Topics: Humans; Dermatitis, Atopic; Child; Female; Adolescent; Male; Singapore; Child, Preschool; Retrospective Studies; Phototherapy; Ultraviolet Therapy
PubMed: 38874329
DOI: 10.1111/phpp.12986 -
Biomedical Materials (Bristol, England) Jun 2024Recently, cytokine-induced killer (CIK) cells have a broad application prospect in the comprehensive diagnosis and treatment of tumors owing to their unique...
Recently, cytokine-induced killer (CIK) cells have a broad application prospect in the comprehensive diagnosis and treatment of tumors owing to their unique characteristics of killing and targeting malignant tumors. Herein, we report a facile strategy for synthesis of monodisperse gold nanostars (GNSs) based on PEGylation and co-loaded with the photosensitizer chlorin e6 (Ce6) to form GNSs-PEG@Ce6 NPs. Then employing CIK cells loading the as-prepared GNSs-PEG@Ce6 NPs to fabricate a CIK cells-based drug delivery system (GNSs-PEG@Ce6-CIK) for lung cancer. Among them, GNSs was functioned as transport media, Ce6 acted as the near-infrared (NIR) fluorescence imaging agent and photodynamic therapy (PDT), and CIK cells served as targeting vectors for immunotherapy, which can increase the efficiency of tumor enrichment and treatment effect. The results of cellular experiments demonstrated that GNSs-PEG@Ce6 NPs had good dispersibility, water solubility and low toxicity under physiological conditions, and the cultured CIK cells had strong anti-tumor properties. Subsequently, GNSs-PEG@Ce6-CIK could effectively inhibit the growth of A549 cells under the exposure of 633 nm laser, which showed stronger killing effect than that of GNSs-PEG@Ce6 NPs or CIK cells. In addition, they showed good tumor targeting and tumor synergistic killing activity. Therefore, GNSs-PEG@Ce6-CIK was constructed for targeted NIR fluorescence imaging, enhanced PDT and immunotherapy of lung cancer.
Topics: Gold; Chlorophyllides; Photochemotherapy; Lung Neoplasms; Humans; Animals; Porphyrins; Cytokine-Induced Killer Cells; Photosensitizing Agents; Metal Nanoparticles; Mice; Immunotherapy; Cell Line, Tumor; Drug Delivery Systems; Polyethylene Glycols; A549 Cells; Optical Imaging; Mice, Nude
PubMed: 38870927
DOI: 10.1088/1748-605X/ad580c -
Nanomaterials (Basel, Switzerland) May 2024Photodynamic therapy (PDT) has developed as an efficient strategy for cancer treatment. PDT involves the production of reactive oxygen species (ROS) by light irradiation...
Photodynamic therapy (PDT) has developed as an efficient strategy for cancer treatment. PDT involves the production of reactive oxygen species (ROS) by light irradiation after activating a photosensitizer (PS) in the presence of O. PS-coupled nanomaterials offer additional advantages, as they can merge the effects of PDT with conventional enabling-combined photo-chemotherapeutics effects. In this work, mesoporous titania nanorods were surface-immobilized with Chlorin e6 (Ce6) conjugated through 3-(aminopropyl)-trimethoxysilane as a coupling agent. The mesoporous nanorods act as nano vehicles for doxorubicin delivery, and the Ce6 provides a visible light-responsive production of ROS to induce PDT. The nanomaterials were characterized by XRD, DRS, FTIR, TGA, N adsorption-desorption isotherms at 77 K, and TEM. The obtained materials were tested for their singlet oxygen and hydroxyl radical generation capacity using fluorescence assays. In vitro cell viability experiments with HeLa cells showed that the prepared materials are not cytotoxic in the dark, and that they exhibit photodynamic activity when irradiated with LED light (150 W m). Drug-loading experiments with doxorubicin (DOX) as a model chemotherapeutic drug showed that the nanostructures efficiently encapsulated DOX. The DOX-nanomaterial formulations show chemo-cytotoxic effects on Hela cells. Combined photo-chemotoxicity experiments show enhanced effects on HeLa cell viability, indicating that the conjugated nanorods are promising for use in combined therapy driven by LED light irradiation.
PubMed: 38869558
DOI: 10.3390/nano14110933 -
Lasers in Medical Science Jun 2024The aim of this systematic review and meta-analysis (SRM) was to evaluate the effectiveness of the adjunctive use of antimicrobial photodynamic therapy (aPDT) in... (Meta-Analysis)
Meta-Analysis Review
The aim of this systematic review and meta-analysis (SRM) was to evaluate the effectiveness of the adjunctive use of antimicrobial photodynamic therapy (aPDT) in non-surgical periodontal treatment (NSPT) in subjects with Human Immunodeficiency Virus (HIV) and periodontitis. This SRM was registered in PROSPERO (CRD42023410180) and followed the guidelines of PRISMA 2020. Searches were performed in different electronic databases. Risk of bias was performed using the Cochrane Risk of Bias tool (RoB 2.0) for randomized clinical trials (RCT). Meta-analysis was performed using Rev Man software. The mean difference (MD) measure of effect was calculated, the random effect model was applied with a 95% confidence interval, and heterogeneity was tested by the I index. The certainty of the evidence was rated using GRADE. A total of 1118 records were screened, and four studies were included. There was a greater reduction in the microbial load of periodontopathogens after NSPT with aPDT. Meta-analysis showed that probing depth (post 3 and 6 months) and clinical attachment loss (post 6 months) were lower for the aPDT-treated group than the NSPT alone: MD -0.39 [-0.74; -0.05], p = 0.02; MD -0.70 [-0.99; -0.41], p < 0.0001; MD -0.84 [-1,34; -0.34], p = 0.0001, respectively. Overall, the studies had a low risk of bias and, the certainty of evidence was rated as moderate. It is suggested that aPDT is a promising adjuvant therapy, showing efficacy in the reduction of the microbial load and in some clinical parameters of individuals with periodontitis and HIV.
Topics: Humans; Photochemotherapy; HIV Infections; Periodontitis; Anti-Infective Agents
PubMed: 38865020
DOI: 10.1007/s10103-024-04087-y -
Molecular Pharmaceutics Jul 2024Cetuximab (Cet)-IRDye800CW, among other antibody-IRDye800CW conjugates, is a potentially effective tool for delineating tumor margins during fluorescence image-guided...
Cetuximab (Cet)-IRDye800CW, among other antibody-IRDye800CW conjugates, is a potentially effective tool for delineating tumor margins during fluorescence image-guided surgery (IGS). However, residual disease often leads to recurrence. Photodynamic therapy (PDT) following IGS is proposed as an approach to eliminate residual disease but suffers from a lack of molecular specificity for cancer cells. Antibody-targeted PDT offers a potential solution for this specificity problem. In this study, we show, for the first time, that Cet-IRDye800CW is capable of antibody-targeted PDT when the payload of dye molecules is increased from 2 (clinical version) to 11 per antibody. Cet-IRDye800CW (1:11) produces singlet oxygen, hydroxyl radicals, and peroxynitrite upon activation with 810 nm light. assays on FaDu head and neck cancer cells confirm that Cet-IRDye800CW (1:11) maintains cancer cell binding specificity and is capable of inducing up to ∼90% phototoxicity in FaDu cancer cells. The phototoxicity of Cet-IRDye800CW conjugates using 810 nm light follows a dye payload-dependent trend. Cet-IRDye800CW (1:11) is also found to be more phototoxic to FaDu cancer cells and less toxic in the dark than the approved chromophore indocyanine green, which can also act as a PDT agent. We propose that antibody-targeted PDT using high-payload Cet-IRDye800CW (1:11) could hold potential for eliminating residual disease postoperatively when using sustained illumination devices, such as fiber optic patches and implantable surgical bed balloon applicators. This approach could also potentially be applicable to a wide variety of resectable cancers that are amenable to IGS-PDT, using their respective approved full-length antibodies as a template for high-payload IRDye800CW conjugation.
Topics: Humans; Photochemotherapy; Indoles; Cetuximab; Cell Line, Tumor; Head and Neck Neoplasms; Photosensitizing Agents; Benzenesulfonates
PubMed: 38861020
DOI: 10.1021/acs.molpharmaceut.4c00046 -
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 -
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