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1.
Int J Nanomedicine ; 15: 5803-5811, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821102

RESUMO

Introduction: Photodynamic therapy (PDT), which induces tissue damage by exposing tissue to a specific wavelength of light in the presence of a photosensitizer and oxygen, is a promising alternative treatment that could be used as an adjunct to chemotherapy and surgery in oncology. Cell-penetrating peptides (CPPs) with high arginine content, such as protamine, have membrane translocation and lysosome localization activities. They have been used in an extensive range of drug delivery applications. Methods: We conjugated cell-penetrating peptides (CPPs) with methylene blue (MB) and then purification by FPLC. Synthesis structure was characterized by the absorbance spectrum, FPLC, Maldi-TOF, and then evaluated cell viability by cytotoxicity assay after photodynamic therapy (PDT) assay. An uptake imaging assay was used to determine the sites of MB and MB-Pro in subcellular compartments. Results: In vitro assays showed that MB-Pro has more efficient photodynamic activities than MB alone for the colon cancer cells, owing to lysosome rupture causing the rapid necrotic cell death. In this study, we coupled protamine with MB for high efficacy PDT. The conjugates localized in the lysosomes and enhanced the efficiency of PDT by inducing necrotic cell death, whereas PDT with non-coupled MB resulted in only apoptotic processes. Discussion: Our research aimed to enhance PDT by engineering the photosensitizers using CPPs coupled with methylene blue (MB). MB alone permeates through the cell membrane and distributes into the cytoplasm, whereas coupling of MB dye with CPPs localizes the MB through an endocytic mechanism to a specific organelle where the localized conjugates enhance the generation of reactive oxygen species (ROS) and induce cell damage.


Assuntos
Peptídeos Penetradores de Células/farmacologia , Azul de Metileno/farmacologia , Fotoquimioterapia , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Células HT29 , Humanos , Imageamento Tridimensional , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Azul de Metileno/química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo
2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(3): 283-288, 2020 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-32616121

RESUMO

Objective To investigate the effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on Propionibacterium acnes (P.acnes) biofilm. Methods P.acnes biofilms were constructed on a cell slide and treated with ALA-PDT.According to different light doses,the biofilms were divided into six groups:ALA-PDT group [ALA-PDT1 (50 J/cm2),ALA-PDT2 group (100 J/cm2),ALA-PDT3 group (200 J/cm2)],ALA-only group (ALA group),light-only group (LED),and a negative control group (ALA-PDT-group).The biofilm structure and the ratio of the dead bacteria/live bacteria were observed using a laser confocal microscope (CLSM).Biofilm viability was measured using the XTT assay. Results CLSM showed that the biofilm structures of ALA group and LED group were not significantly different from that of ALA-PDT-group,whereas the biofilm structure was more seriously damaged in ALA-PDT1 group,ALA-PDT2 group,and ALA-PDT3 group than in the ALA-PDT-group.The ratios of the dead/live bacteria in ALA-PDT-group,ALA group,LED group,ALA-PDT1 group,ALA-PDT2 group,and ALA-PDT3 group were 0.350±0.033, 0.305±0.046, 0.330±0.032, 1.525±0.439, 2.293±0.148 and 3.092±0.189,respectively.ALA group(md=0.003, P=1.000)and LED group(md=-0.025, P=1.000)did not significantly differ from the ALA-PDT-group.However,the ratio of dead/live bacteria in ALA-PDT-group was significantly lower than those in ALA-PDT1 group (md=-0.162, P<0.001),ALA-PDT2 group (md=-0.254, P<0.001),and ALA-PDT3 group (md=-0.352, P<0.001).The values of the XTT assay were were 0.462±0.028,0.465±0.044,0.437±0.047,0.301±0.040,0.207±0.001,and 0.110±0.007,respectively,in ALA-PDT-group,ALA group,LED group,ALA-PDT1 group,ALA-PDT2 group,and ALA-PDT3 group.Although the values of XTT assay in ALA(md=-0.044, P=1.000)and LED groups (md=-0.020, P=1.000)did not significantly differ from that in ALA-PDT-group,it was significantly higher in ALA-PDT-group than in ALA-PDT1 group (md=1.175, P<0.001),ALA-PDT2 group (md=1.942, P<0.001),and ALA-PDT3 group (md=-0.352, md=2.742, P<0.001). Conclusions ALA-PDT has an inhibitory effect on P.acnes biofilm.ALA-PDT destroys biofilm structure and inhibits biofilm viability.


Assuntos
Biofilmes , Ácido Aminolevulínico , Fotoquimioterapia , Fármacos Fotossensibilizantes , Propionibacterium acnes
3.
J Nippon Med Sch ; 87(3): 110-117, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655090

RESUMO

BACKGROUND: Cutaneous wound healing is a complex, dynamic physiological process. Traditional methods of promoting wound healing are not always effective. Consequently, alternative modalities, such as photodynamic therapy (PDT), are needed. We examined the effectiveness and underlying mechanisms of PDT in a murine model of acute wound healing. METHODS: Two excisional wounds were produced, one on each side of the midline, in C57bL/6J mice. Methyl 5-aminolevulinate hydrochloride (MAL) was applied to the right-side wound. After 1 to 3 hours of incubation, the wound was irradiated with red light. The left-side wound was not treated with MAL or red light. On Day 14, the wounds were excised and subjected to histological and immunohistochemical analysis. RESULTS: During the first week, no difference was seen between the two sides. However, at week 2, PDT-treated wounds exhibited delayed re-epithelialization. On Day 14, hematoxylin and eosin (HE) staining showed a continuous epithelial lining in untreated wounds. In contrast, PDT-treated wounds partially lacked epithelium in the wound bed. Masson's Trichrome (MTC) staining showed a thicker dermis and more collagen fibers and inflammatory cells in PDT-treated wounds than in untreated wounds. Immunohistochemical analyses showed significantly fewer CD31+ blood vessels and greater collagen III density in PDT-treated wounds than in untreated wounds. However, treated and untreated wounds did not differ in collagen I density. CONCLUSIONS: PDT delayed acute wound healing in a murine model of secondary intention wound healing.


Assuntos
Fotoquimioterapia/efeitos adversos , Fenômenos Fisiológicos da Pele , Cicatrização/efeitos da radiação , Animais , Colágeno/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Pele/metabolismo , Fatores de Tempo , Cicatrização/fisiologia , Infecção dos Ferimentos
4.
Int J Nanomedicine ; 15: 3405-3414, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32523340

RESUMO

Background: Fluorescent metallic nanodots (NDs) have become a promising nanoprobe for a wide range of biomedical applications. Because Ag NDs have a high tendency to be oxidized, their synthesis and storage are a big challenge. Thus, the method for preparing stable Ag NDs is urgently needed. Surface modification and functionalization can enrich the capability of Ag NDs. Methods: In this work, fluorescent Ag NDs were synthesized in deoxygenated water by using porcine pancreatic α-amylase (PPA) as the stabilizing/capping agent. The absorption and fluorescence of PPA-protected Ag NDs (PPA@AgNDs) were measured with a spectrophotometer and a spectrofluorometer, respectively. The morphology of PPA@AgNDs was characterized by high-angle annular dark-field (HAADF) scanning transmission electron microscopy (STEM). The biocompatibility of PPA@AgNDs was evaluated by tetrazolium (MTT)-based assay. PolyLys-Cys-SH (sequence: KKKKKKC) peptides were conjugated to PPA@AgNDs via heterobifunctional crosslinkers. PolyLys-Cys-linked PPA@AgNDs absorbed 5-aminolevulinic acid (ALA) by electrostatic interaction at physiological pH. The capability of tumor targeting was evaluated by intravenously injecting PPA@AgND-ALA into 4T1 breast cancer xenograft mouse models. Photodynamic therapy (PDT) against tumors was performed under 635 nm laser irradiation. Results: PPA@AgNDs emitted at 640 nm with quantum yield of 2.1%. The Ag NDs exhibited strong photostability over a long period and a fluorescence lifetime of 5.1 ns. PPA@AgNDs easily entered the cells to stain the nuclei, showing the capabilities of living cell imaging with negligible cytotoxicity. ALA-loaded PPA@AgNDs (PPA@AgND-ALA) presented the superiority of passive tumor targeting via the enhanced permeability and retention (EPR) effect. Tumors were visualized in the near-infrared (NIR) region with reduced background noise. ALA molecules released from PPA@AgND-ALA was converted into the photosensitizer (PS) of protoporphyrin IX (PpIX) intracellularly and intratumorally, which greatly improved the PDT efficacy. Conclusion: Our approach opens a new way to design a novel theranostic nanoplatform of PPA@AgND-ALA for effective tumor targeting and fluorescence image-guided PDT.


Assuntos
Amilases/metabolismo , Nanopartículas/química , Neoplasias/tratamento farmacológico , Imagem Óptica , Fotoquimioterapia , Prata/química , Animais , Linhagem Celular Tumoral , Fluorescência , Humanos , Ácidos Levulínicos/farmacologia , Camundongos , Tamanho da Partícula , Espectrofotometria Ultravioleta , Suínos , Nanomedicina Teranóstica , Ensaios Antitumorais Modelo de Xenoenxerto
5.
PLoS One ; 15(6): e0235213, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32579608

RESUMO

PURPOSE: To compare the 1-year visual outcomes and anatomical responses of patients who received photodynamic therapy (PDT) combined with intravitreal ranibizumab (IVR) injections with those of patients who received PDT combined with intravitreal aflibercept (IVA) injections for treating polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively studied all treatment-naïve patients with PCV who received PDT combined with either IVR or IVA. Best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), the number of additional injections, and the presence of polypoidal lesions, as indicated by indocyanine green angiography (ICGA), during 1 year were evaluated. RESULTS: Forty-four eyes were assessed at the 1-year follow-up examination. Of these, 23 were treated with PDT combined with IVR (PDT/IVR group), and 21 were treated with PDT combined with IVA (PDT/IVA group). In both groups, BCVA was shown to be significantly improved 1 year after the initial treatment. CMT and CCT were also significantly decreased after 1 year. There were no significant differences in the changes in BCVA or CMT between the two groups. However, the change in CCT in the PDT/IVA group was significantly larger than that of the PDT/IVR group (P < 0.001). The mean number of additional injections was 0.78 ± 0.21 in the PDT/IVR group and 0.57 ± 0.21 in the PDT/IVA group with no significant difference between the two groups (P = 0.45). The polyp regression rate at 12 months was 78.2% in the PDT/IVR group and 78.9% in the PDT/IVA group with no significant difference between the two groups. CONCLUSIONS: PDT combined with either IVR or IVA was well tolerated and appeared to improve both vision and anatomy in patients with PCV. PDT/IVA may have a more pronounced effect on macular choroidal thickness at 1-year follow-up.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Doenças da Coroide/tratamento farmacológico , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Corioide/fisiologia , Doenças da Coroide/patologia , Terapia Combinada , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Lasers , Masculino , Pessoa de Meia-Idade , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Retrospectivos , Verteporfina/uso terapêutico , Acuidade Visual
6.
Nat Commun ; 11(1): 3262, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32591538

RESUMO

The use of photodynamic therapy (PDT) against cancer has received increasing attention over recent years. However, the application of the currently approved photosensitizers (PSs) is limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum. However, these compounds generally lack significant absorption in the biological spectral window, limiting their application to treat deep-seated or large tumors. To overcome this drawback, ruthenium(II) polypyridine complexes designed in silico with (E,E')-4,4'-bisstyryl-2,2'-bipyridine ligands show impressive 1- and 2-Photon absorption up to a magnitude higher than the ones published so far. While nontoxic in the dark, these compounds are phototoxic in various 2D monolayer cells, 3D multicellular tumor spheroids and are able to eradicate a multiresistant tumor inside a mouse model upon clinically relevant 1-Photon and 2-Photon excitation.


Assuntos
Complexos de Coordenação/uso terapêutico , Desenho de Fármacos , Fotoquimioterapia , Fótons , Rutênio/química , Animais , Proliferação de Células , Sobrevivência Celular , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Feminino , Células HeLa , Humanos , Camundongos Nus , Oxigênio Singlete/química , Análise Espectral , Esferoides Celulares/patologia
7.
ACS Nano ; 14(6): 6383-6406, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32519842

RESUMO

The COVID-19 outbreak has fueled a global demand for effective diagnosis and treatment as well as mitigation of the spread of infection, all through large-scale approaches such as specific alternative antiviral methods and classical disinfection protocols. Based on an abundance of engineered materials identifiable by their useful physicochemical properties through versatile chemical functionalization, nanotechnology offers a number of approaches to cope with this emergency. Here, through a multidisciplinary Perspective encompassing diverse fields such as virology, biology, medicine, engineering, chemistry, materials science, and computational science, we outline how nanotechnology-based strategies can support the fight against COVID-19, as well as infectious diseases in general, including future pandemics. Considering what we know so far about the life cycle of the virus, we envision key steps where nanotechnology could counter the disease. First, nanoparticles (NPs) can offer alternative methods to classical disinfection protocols used in healthcare settings, thanks to their intrinsic antipathogenic properties and/or their ability to inactivate viruses, bacteria, fungi, or yeasts either photothermally or via photocatalysis-induced reactive oxygen species (ROS) generation. Nanotechnology tools to inactivate SARS-CoV-2 in patients could also be explored. In this case, nanomaterials could be used to deliver drugs to the pulmonary system to inhibit interaction between angiotensin-converting enzyme 2 (ACE2) receptors and viral S protein. Moreover, the concept of "nanoimmunity by design" can help us to design materials for immune modulation, either stimulating or suppressing the immune response, which would find applications in the context of vaccine development for SARS-CoV-2 or in counteracting the cytokine storm, respectively. In addition to disease prevention and therapeutic potential, nanotechnology has important roles in diagnostics, with potential to support the development of simple, fast, and cost-effective nanotechnology-based assays to monitor the presence of SARS-CoV-2 and related biomarkers. In summary, nanotechnology is critical in counteracting COVID-19 and will be vital when preparing for future pandemics.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Nanotecnologia/métodos , Pandemias , Pneumonia Viral , Betacoronavirus/genética , Betacoronavirus/imunologia , Biomimética , Simulação por Computador , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Desinfecção , Sistemas de Liberação de Medicamentos , Microbiologia Ambiental , Humanos , Imunomodulação , Máscaras , Nanomedicina , Nanotecnologia/tendências , Pandemias/prevenção & controle , Equipamento de Proteção Individual , Fotoquimioterapia , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Vacinas Virais/genética , Vacinas Virais/farmacologia
8.
Life Sci ; 255: 117858, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32497635

RESUMO

At present, cervical cancer is the fourth leading cause of cancer among women worldwide with no effective treatment options. In this study we aimed to evaluate the efficacy of hypericin (HYP) encapsulated on Pluronic® P123 (HYP/P123) photodynamic therapy (PDT) in a comprehensive panel of human cervical cancer-derived cell lines, including HeLa (HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and 18-positive), and C33A (HPV-negative), compared to a nontumorigenic human epithelial cell line (HaCaT). Were investigated: (i) cell cytotoxicity and phototoxicity, cellular uptake and subcellular distribution; (ii) cell death pathway and cellular oxidative stress; (iii) migration and invasion. Our results showed that HYP/P123 micelles had effective and selective time- and dose-dependent phototoxic effects on cervical cancer cells but not in HaCaT. Moreover, HYP/P123 micelles accumulated in endoplasmic reticulum, mitochondria and lysosomes, resulting in photodynamic cell death mainly by necrosis. HYP/P123 induced cellular oxidative stress mainly via type II mechanism of PDT and inhibited cancer cell migration and invasion mainly via MMP-2 inhibition. Taken together, our results indicate a potentially useful role of HYP/P123 micelles as a platform for HYP delivery to more specifically and effectively treat cervical cancers through PDT, suggesting they are worthy for in vivo preclinical evaluations.


Assuntos
Antineoplásicos/administração & dosagem , Nanopartículas , Perileno/análogos & derivados , Fotoquimioterapia/métodos , Neoplasias do Colo do Útero/tratamento farmacológico , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Feminino , Células HeLa , Humanos , Micelas , Invasividade Neoplásica , Estresse Oxidativo/efeitos dos fármacos , Perileno/administração & dosagem , Perileno/farmacologia , Poloxaleno/química , Fatores de Tempo , Neoplasias do Colo do Útero/patologia
9.
Pestic Biochem Physiol ; 167: 104584, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32527419

RESUMO

Recently, photodynamic therapy (PDT) and photoactivated pesticides have attracted considerable research attention. In the present study, we aimed to investigate the photodynamic activity of a chlorophyllous derivative, sodium pheophorbide a (SPA), and to evaluate its potential as a photoactivated fungicide. The singlet oxygen quantum yield, the photoreaction process, the anti-photobleaching ability in sterile water (H2O), the effect of light conditions on its antifungal activity, and its stability were all investigated. SPA showed significant fungicidal activity and photostability, during which Type I and Type II photodynamic reactions occurred simultaneously on Pestalotiopsis neglecta, and the influence of Type I was slightly larger than that of Type II. In addition, light promoted the antifungal activity of SPA. In particular, the antifungal activity was enhanced with increasing light intensity, and was strongest under 8000 lx conditions. Under monochromatic light sources, antifungal activity was strongest under green light s; however, the effect of monochromatic light was not as good as that of white light. From 0 to 24 h, the antifungal effect of the SPA solution was enhanced; however, the activity of the solution began to weaken after 24 h. Furthermore, our study confirmed that the antifungal activity of SPA was stable under different temperatures, pH values, and UV irradiation durations.


Assuntos
Fotoquimioterapia , Sódio , Antifúngicos , Clorofila/análogos & derivados , Fármacos Fotossensibilizantes
10.
Int J Nanomedicine ; 15: 3023-3038, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431499

RESUMO

Introduction: Advanced tumor-targeted theranostic nanoparticles play a key role in tumor diagnosis and treatment research. In this study, we developed a multifunctional theranostic platform based on an amphiphilic hyaluronan/poly-(N-ε-carbobenzyloxy-L-lysine) derivative (HA-g-PZLL), superparamagnetic iron oxide (SPIO) and aggregation-induced emission (AIE) nanoparticles for tumor-targeted magnetic resonance (MR) and fluorescence (FL) dual-modal image-guided photodynamic therapy (PDT). Materials and Methods: The amphiphilic hyaluronan acid (HA) derivative HA-g-PZLL was synthesized by grafting hydrophobic poly-(N-ε-carbobenzyloxy-L-lysine) (PZLL) blocks onto hyaluronic acid by a click conjugation reaction. The obtained HA-g-PZLLs self-assembled into nanoparticles in the presence of AIE molecules and SPIO nanoparticles to produce tumor-targeted theranostic nanoparticles (SPIO/AIE@HA-g-PZLLs) with MR/FL dual-modal imaging ability. Cellular uptake of the theranostic nanoparticles was traced by confocal laser scanning microscopy (CLSM), flow cytometry and Prussian blue staining. The intracellular reactive oxygen species (ROS) generation characteristics of the theranostic nanoparticles were evaluated with CLSM and flow cytometry. The effect of PDT was evaluated by cytotoxicity assay. The dual-mode imaging ability of the nanoparticles was evaluated by a real-time near-infrared fluorescence imaging system and magnetic resonance imaging scanning. Results: The resulting theranostic nanoparticles not only emit red fluorescence for high-quality intracellular tracing but also effectively produce singlet oxygen for photodynamic tumor therapy. In vitro cytotoxicity experiments showed that these theranostic nanoparticles can be efficiently taken up and are mainly present in the cytoplasm of HepG2 cells. After internalization, these theranostic nanoparticles showed serious cytotoxicity to the growth of HepG2 cells after white light irradiation. Discussion: This work provides a simple method for the preparation of theranostic nanoparticles with AIE characteristics and MR contrast enhancement, and serves as a dual-modal imaging platform for image-guided tumor PDT.


Assuntos
Meios de Contraste/química , Imagem por Ressonância Magnética , Nanopartículas/química , Imagem Óptica , Fotoquimioterapia , Nanomedicina Teranóstica , Animais , Linhagem Celular Tumoral , Feminino , Fluorescência , Células Hep G2 , Humanos , Ácido Hialurônico/síntese química , Ácido Hialurônico/química , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Polilisina/síntese química , Polilisina/química , Espectroscopia de Prótons por Ressonância Magnética , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier
11.
Vestn Oftalmol ; 136(2): 99-106, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32366077

RESUMO

Corneal collagen cross-linking (CXL) is a procedure that aims to halt the progression of corneal ectasia in keratoconic eyes. It is achieved by inducing cross-links in the corneal stroma and extracellular matrix by exposing it to ultraviolet-A (370 nm) irradiation while it is filled with photosensitizer (riboflavin). According to the conventional protocol, the recommended de-epithelialized corneal thickness should be higher than 400 µm in order to avoid radiation damage to the corneal endothelium. However, in progressive keratoconus, corneal thickness is often close to or lower than this threshold of 400 µm, which limits the application of cross-linking for these patients. The present article reviews the different protocols of cross-linking for thin corneas, their advantages and disadvantages. At present, clinical research on modified cross-linking protocols is still limited due to the methodology and a low number of patients involved. Thus, comparative randomized controlled studies with long-term follow-up are necessary to confirm the safety and effectiveness of several CXL protocols and identify the most efficient one.


Assuntos
Ceratocone , Córnea , Substância Própria , Reagentes para Ligações Cruzadas , Humanos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Riboflavina , Raios Ultravioleta
13.
PLoS One ; 15(5): e0232775, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32374766

RESUMO

Antibacterial photodynamic therapy (aPDT) and antibacterial blue light (aBL) are emerging treatment methods auxiliary to mechanical debridement for periodontitis. APDT provided with near-infrared (NIR) light in conjunction with an indocyanine green (ICG) photosensitizer has shown efficacy in several dental in-office-treatment protocols. In this study, we tested Streptococcus mutans biofilm sensitivity to either aPDT, aBL or their combination dual-light aPDT (simultaneous aPDT and aBL) exposure. Biofilm was cultured by pipetting diluted Streptococcus mutans suspension with growth medium on the bottom of well plates. Either aPDT (810 nm) or aBL (405 nm) or a dual-light aPDT (simultaneous 810 nm aPDT and 405 nm aBL) was applied with an ICG photosensitizer in cases of aPDT or dual-light, while keeping the total given radiant exposure constant at 100 J/cm2. Single-dose light exposures were given after one-day or four-day biofilm incubations. Also, a model of daily treatment was provided by repeating the same light dose daily on four-day and fourteen-day biofilm incubations. Finally, the antibacterial action of the dual-light aPDT with different energy ratios of 810 nm and 405 nm of light were examined on the single-day and four-day biofilm protocols. At the end of each experiment the bacterial viability was assessed by colony-forming unit method. Separate samples were prepared for confocal 3D biofilm imaging. On a one-day biofilm, the dual-light aPDT was significantly more efficient than aBL or aPDT, although all modalities were bactericidal. On a four-day biofilm, a single exposure of aPDT or dual-light aPDT was more efficient than aBL, resulting in a four logarithmic scale reduction in bacterial counts. Surprisingly, when the same amount of aPDT was repeated daily on a four-day or a fourteen-day biofilm, bacterial viability improved significantly. A similar improvement in bacterial viability was observed after repetitive aBL application. This viability improvement was eliminated when dual-light aPDT was applied. By changing the 405 nm to 810 nm radiant exposure ratio in dual-light aPDT, the increase in aBL improved the antibacterial action when the biofilm was older. In conclusion, when aPDT is administered repeatedly to S. mutans biofilm, a single wavelength-based aBL or aPDT leads to a significant biofilm adaptation and increased S. mutans viability. The combined use of aBL light in synchrony with aPDT arrests the adaptation and provides significantly improved and sustained antibacterial efficacy.


Assuntos
Adaptação Biológica/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Verde de Indocianina/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Streptococcus mutans/efeitos dos fármacos , Adaptação Biológica/efeitos da radiação , Carga Bacteriana/efeitos dos fármacos , Carga Bacteriana/efeitos da radiação , Biofilmes/efeitos da radiação , Humanos , Viabilidade Microbiana/efeitos dos fármacos , Viabilidade Microbiana/efeitos da radiação , Higiene Bucal/métodos , Periodontite/tratamento farmacológico , Streptococcus mutans/efeitos da radiação
14.
Photodiagnosis Photodyn Ther ; 31: 101804, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32437972

RESUMO

•The World today is facing a great effort for the control of infections.•Nowadays COVID-19 is the large global outbreak and is the major public health issue.•This letter to Editor highlighted the well-established photodynamic therapy protocol as a tool to decrease the viral and bacterial load in the respiratory tract.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Fotoquimioterapia/métodos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Infecções Respiratórias/tratamento farmacológico , Betacoronavirus , Humanos , Pandemias , Fármacos Fotossensibilizantes
15.
Cutis ; 105(3): 138-142;E5, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32352432

RESUMO

Nonmelanoma skin cancer (NMSC) is the most common malignancy worldwide, and the incidence continues to increase. Originally, treatment options for NMSCs largely relied on destructive and surgical methods. Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) commonly are treated with cryosurgery, electrodesiccation and curettage, or more definitive surgical options. Over time, topical agents such as 5-fluorouracil, imiquimod, ingenol mebutate, and various forms of aminolevulinic acid (ALA) for photodynamic therapy (PDT) were included for superficial lesions as well as field treatment. The development of oral hedgehog (Hh) inhibitors such as vismodegib offered a promising alternative to patients with advanced disease. Each treatment has its own specific indications and side effects, thus there is always room for novel therapeutic approaches. We review new and potential treatments for NMSCs since 2018 including topical sonidegib, cemiplimab, taladegib, posaconazole, radiation therapy (RT), combination RT with vismodegib, PDT, and laser therapies.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Basocelular/terapia , Carcinoma de Células Escamosas/terapia , Neoplasias Cutâneas/terapia , Carcinoma Basocelular/metabolismo , Carcinoma de Células Escamosas/metabolismo , Humanos , Terapia a Laser , Fotoquimioterapia , Radioterapia , Neoplasias Cutâneas/metabolismo
16.
Cell Prolif ; 53(5): e12821, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32364266

RESUMO

OBJECTIVES: Photodynamic therapy (PDT) is a promising approach for cancer treatment, and the underlying signalling pathway changes has been carried out for studying the PDT mechanisms, but is majorly limited to organic photosensitizers (PSs). For the emerging nano-PSs typically possessing higher 1 O2 quantum yield, few mechanistic studies were carried out, which limited their further applications in clinical therapeutics. PI3K/Akt signalling pathway, a most frequently activated signalling network in cancers, could promote cancer cell survival, but was seldom reported in previous PDT studies mediated by nano-PSs. MATERIALS AND METHODS: Sulphur doped carbon dots (S-CDs) was prepared via a hydrothermal synthetic route and was characterized by transmission electron microscopy, X-ray photoelectron spectroscopy and so on. CCK-8 assay and Annexin V/PI staining were performed to demonstrate the death of cancer cells, Western blot, RT-PCR and immunofluorescence were employed to explore the underlying mechanism, and variation of PI3K/Akt and other signalling pathways was detected by Western blot. RESULTS: S-CDs was successfully synthesized, and it was much more efficient compared with classic organic PSs. S-CDs could induce cancer cell death through mitochondria mediated cell apoptosis with the imbalance of Bcl-2 family proteins and caspase cascade via several signalling pathways. Low concentration of S-CDs could effectively inhibit PI3K/Akt pathway and promote p38/JNK pathway, on one way inhibiting cancer cell survival and on the other way promoting cell apoptosis. CONCLUSIONS: Herein, we found that S-CDs acted as an inhibitor of the PI3K/Akt pathway for efficient cancer cell killing, thus yielding in a higher PDT performance over the existing photosensitizers.


Assuntos
Carbono/farmacologia , Neoplasias/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Enxofre/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neoplasias/metabolismo , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
17.
J Contemp Dent Pract ; 21(1): 11-16, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32381794

RESUMO

AIM: To compare the antimicrobial effects of two different irrigation solutions activated with erbium, chromium-doped yttrium, scandium, gallium and garnet (Er,Cr:YSGG) laser or an ultrasonic system and a photodynamic therapy (PDT) on Enterococcus faecalis (E. faecalis). MATERIALS AND METHODS: The root canals of 72 single-rooted human permanent incisors were prepared with ProTaper Universal rotary instruments and incubated with E. faecalis (ATCC 29212) for 4 weeks. Then the teeth were randomly divided into seven experimental groups with 10 specimens for canal disinfection procedures. Group I, standard needle irrigation (SNI) with 2.5% sodium hypochlorite (NaOCl); group II, SNI with 2% chlorhexidine gluconate (CHX); group III, laser-activated irrigation (LAI) by Er,Cr:YSGG of NaOCl; group IV, LAI of CHX; and group V, passive ultrasonic irrigation (PUI) of NaOCl; group VI, PUI of CHX; group VII, PDT. The remaining two teeth were used as the control group. After the disinfection procedures were completed, the root canals were filled with phosphate-buffered saline and bacterial samples were taken with sterile paper cones. The cultivation was performed on Mueller-Hinton agar (MHA) plates. The live bacteria were calculated by counting the colonies on these plaques. The statistical analysis was performed using Kruskal-Wallis H test and Miller's multiple comparison technique. RESULTS: Both LAI and PUI of NaOCl and PUI of CHX were more successful than the PDT on root canal disinfection (p < 0.05). CONCLUSION: Within the limitation of the present study, the activation of NaOCl solution by Er,Cr:YSGG laser or an ultrasonic system can be useful in the elimination of the E. faecalis from the canal. The PUI of CHX also has similar results. Photodynamic therapy showed a lower performance compared to these methods. CLINICAL SIGNIFICANCE: The activation of the sodium hypochlorite with Er,Cr:YSGG laser or PUI may be useful for removal of the E. faecalis biofilm layer in the root canal.


Assuntos
Gálio , Fotoquimioterapia , Cromo , Cavidade Pulpar , Enterococcus faecalis , Érbio , Humanos , Irrigantes do Canal Radicular , Escândio , Ultrassom , Ítrio
19.
PLoS One ; 15(4): e0231439, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298314

RESUMO

INTRODUCTION: The primary purpose of crosslinking is to halt the progression of ectasia. We retrospectively assessed the condition of keratoconus patients who were followed-up at least twice after the initial examination to evaluate keratoconus progression, to identify definitive factors to predict a later need for corneal crosslinking (CXL). METHODS: The medical charts of 158 eyes of 158 keratoconus patients (112 males and 46 females; mean age, 27.8 ± 11.7 years), who were followed up at the Department of Ophthalmology, Keio University School of Medicine at least twice after the initial examination to evaluate keratoconus progression were retrospectively reviewed. Best-spectacle corrected visual acuity, intraocular pressure, steepest corneal axis on the anterior float (Ks), thinnest corneal thickness according to Pentacam® HR, and corneal endothelial cell density were assessed. Gender, age, onset age of keratoconus, history of atopic dermatitis, and Pentacam® indices were also recorded. CXL was performed when the eye showed significant keratoconus progression, an increase in the steepest keratometric value, or an increase in the spherical equivalent or cylinder power of the manifest refraction by more than 1.0 D versus the respective values 2 years prior. Predictor variables and the requirement for CXL were analyzed using logistic regression. RESULTS: Fifty-eight eyes required CXL treatment. The best predictor of the requirement for CXL was patient age, followed by the Pentacam® Rmin (the minimum sagittal curvature evaluated by Pentacam®) value. The incidence of CXL was 86.4% in the < 20 years age group, with an Rmin of ≤ 5.73 mm, whereas 10.8% in the ≥ 27 years age group with an Rmin > 5.73 mm underwent treatment. CONCLUSIONS: An age of < 20 years and an Rmin value of ≤ 5.73 mm predicted keratoconus progression and the requirement for CXL treatment in the near future.


Assuntos
Ceratocone/patologia , Fotoquimioterapia/métodos , Adolescente , Adulto , Fatores Etários , Reagentes para Ligações Cruzadas/uso terapêutico , Feminino , Humanos , Ceratocone/tratamento farmacológico , Ceratocone/epidemiologia , Ceratocone/radioterapia , Masculino , Fotoquimioterapia/normas , Fármacos Fotossensibilizantes/uso terapêutico , Riboflavina/uso terapêutico , Terapia Ultravioleta
20.
Cell Prolif ; 53(4): e12786, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32301195

RESUMO

OBJECTIVES: Photodynamic therapy (PDT) is a novel non-invasive therapeutic method, which has been widely applied for the treatment of human oral cancers. However, the problems of undesirable singlet oxygen (1 O2 ) quantum yields and long-term phototoxicity were inevitable during the application of traditional photosensitizers. Therefore, it is necessary to explore novel photosensitizers for the improvement of therapeutic effects. In our study, the sulphur-doped carbon dots (S-CDs) of high yield of singlet oxygen (1 O2 ) were synthesized as a nano-photosensitizer for OSCC to improve the PDT efficacy in clinical practice. MATERIALS AND METHODS: After synthesis of the novel S-CDs, the size, morphologic characteristics, surface potential and yield of singlet oxygen (1 O2 ) were determined. In vitro study was performed to compare the therapeutic effect as well as the biocompatibility of the novel S-CDs to those of 5-ALA. Besides, possible mechanism of action was illustrated. RESULTS: After synthesis of the novel S-CDs, the size, morphologic characteristics, surface potential and yield of singlet oxygen (1 O2 ) were determined. In vitro study was performed to compare the therapeutic effect as well as the biocompatibility of the novel S-CDs to those of 5-ALA. Besides, possible mechanism of action was illustrated. CONCLUSIONS: These data from the in vitro study demonstrated the promising safety profile of the low dose (nmol/L) S-CDs, which indicated the novel S-CDs could be used as a promising photodynamic agent for oral cancer therapy.


Assuntos
Carbono/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Enxofre/farmacologia , Apoptose/efeitos dos fármacos , Carbono/química , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Humanos , Modelos Moleculares , Neoplasias Bucais/patologia , Nanopartículas/química , Nanopartículas/ultraestrutura , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Enxofre/química
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