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1.
Nat Commun ; 12(1): 5243, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475406

RESUMO

Peroxisome, a special cytoplasmic organelle, possesses one or more kinds of oxidases for hydrogen peroxide (H2O2) production and catalase for H2O2 degradation, which serves as an intracellular H2O2 regulator to degrade toxic peroxides to water. Inspired by this biochemical pathway, we demonstrate the reactive oxygen species (ROS) induced tumor therapy by integrating lactate oxidase (LOx) and catalase (CAT) into Fe3O4 nanoparticle/indocyanine green (ICG) co-loaded hybrid nanogels (designated as FIGs-LC). Based on the O2 redistribution and H2O2 activation by cascading LOx and CAT catalytic metabolic regulation, hydroxyl radical (·OH) and singlet oxygen (1O2) production can be modulated for glutathione (GSH)-activated chemodynamic therapy (CDT) and NIR-triggered photodynamic therapy (PDT), by manipulating the ratio of LOx and CAT to catalyze endogenous lactate to produce H2O2 and further cascade decomposing H2O2 into O2. The regulation reactions of FIGs-LC significantly elevate the intracellular ROS level and cause fatal damage to cancer cells inducing the effective inhibition of tumor growth. Such enzyme complex loaded hybrid nanogel present potential for biomedical ROS regulation, especially for the tumors with different redox state, size, and subcutaneous depth.


Assuntos
Antineoplásicos/farmacologia , Nanogéis/química , Peroxissomos/enzimologia , Fotoquimioterapia/métodos , Animais , Antineoplásicos/química , Catalase/química , Catalase/metabolismo , Catálise , Linhagem Celular Tumoral , Óxido Ferroso-Férrico/química , Glutationa/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Verde de Indocianina/química , Camundongos , Oxigenases de Função Mista/química , Oxigenases de Função Mista/metabolismo , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Oxigênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Microambiente Tumoral/efeitos dos fármacos
2.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361793

RESUMO

The pretargeting strategy has recently emerged in order to overcome the limitations of direct targeting, mainly in the field of radioimmunotherapy (RIT). This strategy is directly dependent on chemical reactions, namely bioorthogonal reactions, which have been developed for their ability to occur under physiological conditions. The Staudinger ligation, the copper catalyzed azide-alkyne cycloaddition (CuAAC) and the strain-promoted [3 + 2] azide-alkyne cycloaddition (SPAAC) were the first bioorthogonal reactions introduced in the literature. However, due to their incomplete biocompatibility and slow kinetics, the inverse-electron demand Diels-Alder (IEDDA) reaction was advanced in 2008 by Blackman et al. as an optimal bioorthogonal reaction. The IEDDA is the fastest bioorthogonal reaction known so far. Its biocompatibility and ideal kinetics are very appealing for pretargeting applications. The use of a trans-cyclooctene (TCO) and a tetrazine (Tz) in the reaction encouraged researchers to study them deeply. It was found that both reagents are sensitive to acidic or basic conditions. Furthermore, TCO is photosensitive and can be isomerized to its cis-conformation via a radical catalyzed reaction. Unfortunately, the cis-conformer is significantly less reactive toward tetrazine than the trans-conformation. Therefore, extensive research has been carried out to optimize both click reagents and to employ the IEDDA bioorthogonal reaction in biomedical applications.


Assuntos
Antineoplásicos/química , Química Click/métodos , Terapia de Alvo Molecular/métodos , Neoplasias/terapia , Radiossensibilizantes/química , Radioimunoterapia/métodos , Alcinos/química , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/farmacologia , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Azidas/química , Reação de Cicloadição/métodos , Ciclo-Octanos/química , Elétrons , Compostos Heterocíclicos com 1 Anel/química , Humanos , Concentração de Íons de Hidrogênio , Imunoconjugados/química , Imunoconjugados/farmacocinética , Imunoconjugados/farmacologia , Neoplasias/química , Neoplasias/imunologia , Neoplasias/patologia , Fotoquimioterapia/métodos , Radiossensibilizantes/farmacocinética , Radiossensibilizantes/farmacologia
3.
Nat Commun ; 12(1): 4777, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362904

RESUMO

The modulation of intracellular reactive oxygen species (ROS) levels is crucial for cellular homeostasis and determination of cellular fate. A sublethal level of ROS sustains cell proliferation, differentiation and promotes tumor metastasis, while a drastic ROS burst directly induces apoptosis. Herein, surface-oxidized arsenene nanosheets (As/AsxOy NSs) with type II heterojunction are fabricated with efficient ·O2- and 1O2 production and glutathione consumption through prolonging the lifetime of photo-excited electron-hole pairs. Moreover, the portion of AsxOy with oxygen vacancies not only catalyzes a Fenton-like reaction, generating ·OH and O2 from H2O2, but also inactivates main anti-oxidants to cut off the "retreat routes" of ROS. After polydopamine (PDA) and cancer cell membrane (M) coating, the engineered As/AsxOy@PDA@M NSs serve as an intelligent theranostic platform with active tumor targeting and long-term blood circulation. Given its narrow-band-gap-enabled in vivo fluorescence imaging properties, As/AsxOy@PDA@M NSs could be applied as an imaging-guided non-invasive and real-time nanomedicine for cancer therapy.


Assuntos
Nanomedicina , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Células A549 , Animais , Apoptose , Arsênio , Catálise , Linhagem Celular Tumoral , Glutationa/metabolismo , Homeostase , Humanos , Peróxido de Hidrogênio , Indóis , Células MCF-7 , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas , Oxigênio , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros , Medicina de Precisão , Nanomedicina Teranóstica/métodos
4.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360872

RESUMO

Despite the numerous available treatments for cancer, many patients succumb to side effects and reoccurrence. Zinc oxide (ZnO) quantum dots (QDs) are inexpensive inorganic nanomaterials with potential applications in photodynamic therapy. To verify the photoluminescence of ZnO QDs and determine their inhibitory effect on tumors, we synthesized and characterized ZnO QDs modified with polyvinylpyrrolidone. The photoluminescent properties and reactive oxygen species levels of these ZnO/PVP QDs were also measured. Finally, in vitro and in vivo experiments were performed to test their photodynamic therapeutic effects in SW480 cancer cells and female nude mice. Our results indicate that the ZnO QDs had good photoluminescence and exerted an obvious inhibitory effect on SW480 tumor cells. These findings illustrate the potential applications of ZnO QDs in the fields of photoluminescence and photodynamic therapy.


Assuntos
Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Povidona , Pontos Quânticos/uso terapêutico , Óxido de Zinco , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Nus , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/farmacologia , Povidona/química , Povidona/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Óxido de Zinco/química , Óxido de Zinco/farmacologia
5.
Molecules ; 26(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34361832

RESUMO

In recent times, researchers have aimed for new strategies to combat cancer by the implementation of nanotechnologies in biomedical applications. This work focuses on developing protein-based nanoparticles loaded with a newly synthesized NIR emitting and absorbing phthalocyanine dye, with photodynamic and photothermal properties. More precisely, we synthesized highly reproducible bovine serum albumin-based nanoparticles (75% particle yield) through a two-step protocol and successfully encapsulated the NIR active photosensitizer agent, achieving a good loading efficiency of 91%. Making use of molecular docking simulations, we confirm that the NIR photosensitizer is well protected within the nanoparticles, docked in site I of the albumin molecule. Encouraging results were obtained for our nanoparticles towards biomedical use, thanks to their negatively charged surface (-13.6 ± 0.5 mV) and hydrodynamic diameter (25.06 ± 0.62 nm), favorable for benefitting from the enhanced permeability and retention effect; moreover, the MTT viability assay upholds the good biocompatibility of our NIR active nanoparticles. Finally, upon irradiation with an NIR 785 nm laser, the dual phototherapeutic effect of our NIR fluorescent nanoparticles was highlighted by their excellent light-to-heat conversion performance (photothermal conversion efficiency 20%) and good photothermal and size stability, supporting their further implementation as fluorescent therapeutic agents in biomedical applications.


Assuntos
Indóis/administração & dosagem , Nanopartículas/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Soroalbumina Bovina/química , Proliferação de Células , Feminino , Humanos , Indóis/química , Luz , Simulação de Acoplamento Molecular , Nanopartículas/química , Neoplasias Ovarianas/patologia , Fármacos Fotossensibilizantes/química , Espectroscopia de Luz Próxima ao Infravermelho , Células Tumorais Cultivadas
6.
Photodiagnosis Photodyn Ther ; 35: 102469, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34333143

RESUMO

AIM: The present study aimed to assess the push-out bond strength (PBS) and failure modes of fiber-posts after photodynamic therapy (PDT) and Erbium yttrium scandium gallium garnet (Er,Cr:YSGG) in c-shaped canals. METHODS: Sixty molars with c-shaped root configuration were studied. The endodontic prepared teeth specimen were equally randomized into four groups: i) photodynamic therapy (PDT); ii) Er,Cr:YSGG; iii) chlorhexidine and; iv) control group. Post root filling, 10 mm space was prepared for insertion of post in the root canals. The push-out bond strength was evaluated using Universal testing machine. Modes of failure were evaluated as adhesive, cohesive and admixed. Mean values were computed between groups using Kruskal-Wallis test followed by Bonferroni post hoc test. Comparison between two thirds of root sections were analyzed using Friedman test. P-value was set at 0.05 or less. RESULTS: Specimens treated with PDT reported the highest mean PBS (8.56 ± 2.12 MPa), while the lowest PBS was observed in NaOCl group (6.92 ± 2.21 MPa). Thirteen failures were observed at the adhesive post interface, whereas 22 failures were found at the interface forming between the dentin surface and adhesive. Similarly, 9 failures were categorized as mixed. For PDT group, a sum of 3 failures and 4 failures were noted at the apical and cervical points. CONCLUSION: The specimens treated with PDT showed the highest push out bond strength with least number of failures.in c-shaped root canals.


Assuntos
Fotoquimioterapia , Adesivos , Cavidade Pulpar , Dentina , Teste de Materiais , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico
7.
Photodiagnosis Photodyn Ther ; 35: 102465, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34333146

RESUMO

OBJECTIVES: This is a randomized controlled clinical trial comparing Photodynamic Therapy (PDT) and the application of trichloracetic acid (TAA) in the treatment of HPV condyloma in the perianal and vulva regions. Design, Randomised controlled, open label, trial. They were allocated to each treatment following randomization by a computer program. SETTING: Women Health Ambulatory in São Carlos city, São Paulo State in the Brazil. PARTICIPANTS: 36 patients evaluated. 31 patients fulfilled the study requirements. INTERVENTION: Photodynamic Therapy (PDT) versus trichloracetic acid (TAA). The PDT protocol used the prodrug methyl aminolevulinate incubated for 3 hours and irradiation at 630 nm (100 J/cm²). In the treatment using TAA, warts received a small amount of acid using a cotton swab. Both treatments were repeated weekly until the lesions disappeared completely or until 10 sessions were completed. MAIN OUTCOME MEASURE: Clinical analysis. Follow-up between 12 and 30 months after the complete treatment. RESULTS: A total of 16 patients were treated with PDT and 15 patients with TAA. A complete response rate of 60% for TAA and 63% for PDT, with a recurrence rate of 33% for TAA and 0% for PDT. CONCLUSION: PDT appears not only to treat lesions due to physical destruction of condyloma and subclinical lesions, but also to modulate the immune system and/or also to decrease the local viral load, suggesting a lower recurrence compared to the TAA group.


Assuntos
Condiloma Acuminado , Infecções por Papillomavirus , Fotoquimioterapia , Ácido Aminolevulínico/uso terapêutico , Brasil , Condiloma Acuminado/tratamento farmacológico , Feminino , Humanos , Infecções por Papillomavirus/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Ácido Tricloroacético/uso terapêutico
8.
Photodiagnosis Photodyn Ther ; 35: 102471, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34343667

RESUMO

Nanotechnologyapplications in the field of biomedicine like drug delivery, cell labeling, and bacterial inhibition are growing . New nano-materials having less toxicity and excellent antibacterial activity attract research interest. In the current study, while taking advantage of green synthesis we have decorated zinc oxide on the surface of grephene oxide forming Zno@GO nanocomposite. The Transmission electron microscopy (TEM) study showed successfully synthesized trigonal small sizes ZnO on the surface of GO nanosheets. The as-synthesized ZnO@GO was used against MDR gram-negative pathogen E-coli (BL21 DE3) and showed excellent antibacterial activity killing about 95 % toxic bacteria within 5 h due to electrostatic interaction between cell membrane of E. coli (BL21 DE3) and ZnO@GO complex. Hence the nano composite subsequently penetrated into the cytoplasm by damaging the cell membrane of bacteria, as a result production of ROS into the cytoplasm led to imbalance of metabolic system in the cell. Moreover, the cell membrane damage of gram-negative bacteria verified through zeta potential and propidium iodide (PI) study. Thus, our study develops a way to solve the challenge of efficient design of a drug delivery system for dissolution enhancement according to the need for required drug release.


Assuntos
Grafite , Nanocompostos , Fotoquimioterapia , Óxido de Zinco , Antibacterianos/farmacologia , Escherichia coli , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes
9.
Photodiagnosis Photodyn Ther ; 35: 102466, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34343668

RESUMO

Metallic nanostructures can improve the production of singlet oxygen (1O2) of a photosensitizer during photodynamic therapy (PDT) . Engineering a high performance nanoparticle is mandatory for an appropriate use of plasmonic nanostructures in PDT. Metal enhanced singlet oxygen generation requires the use of nanoparticles with high scattering efficiency, capable of inducing a significant electric field enhancement and with plasmon peak overlapping the photosensitizer absorption spectrum. Herein, we report the optimization of nanoshells structure (silica core radius and gold shell thickness) to increase the singlet oxygen production by Methylene Blue photosensitizer. A 3D Full-wave field analysis was used to evaluate the plasmonic spectrum, scattering efficiency and localized field intensity of Au nanoshells as a function of their dimensions. The 40/20 core radius/shell thickness optimized gold nanoshell showed 75% scattering efficiency and field enhancement up to 35 times. Metal-enhanced singlet oxygen generation was observed and quantified for Methylene Blue water solution with gold nanoshell particles. Moreover, the influence of the irradiation time and the metallic nanostructures concentration on metal enhanced singlet oxygen generation were also appraised. The experimental results showed that the use of gold nanoshell improved 320% the 1O2 production in a MB solution. The approach used to select a high performance metallic nanoparticle provides insights on engineering plasmonic structures for metal enhanced singlet oxygen generation for PDT.


Assuntos
Nanopartículas Metálicas , Nanoconchas , Fotoquimioterapia , Ouro , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Oxigênio Singlete
10.
Photodiagnosis Photodyn Ther ; 35: 102473, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34348186

RESUMO

BACKGROUND: The recent emergence of a highly infectious and contagious respiratory viral disease known as COVID-19 has vastly impacted human lives and overloaded the health care system. Therefore, it is crucial to develop a fast and accurate diagnostic system for the timely identification of COVID-19 infected patients and thus to help control its spread. METHODS: This work proposes a new deep CNN based technique for COVID-19 classification in X-ray images. In this regard, two novel custom CNN architectures, namely COVID-RENet-1 and COVID-RENet-2, are developed for COVID-19 specific pneumonia analysis. The proposed technique systematically employs Region and Edge-based operations along with convolution operations. The advantage of the proposed idea is validated by performing series of experimentation and comparing results with two baseline CNNs that exploited either a single type of pooling operation or strided convolution down the architecture. Additionally, the discrimination capacity of the proposed technique is assessed by benchmarking it against the state-of-the-art CNNs on radiologist's authenticated chest X-ray dataset. Implementation is available at https://github.com/PRLAB21/Coronavirus-Disease-Analysis-using-Chest-X-Ray-Images. RESULTS: The proposed classification technique shows good generalization as compared to existing CNNs by achieving promising MCC (0.96), F-score (0.98) and Accuracy (98%). This suggests that the idea of synergistically using Region and Edge-based operations aid in better exploiting the region homogeneity, textural variations, and region boundary-related information in an image, which helps to capture the pneumonia specific pattern. CONCLUSIONS: The encouraging results of the proposed classification technique on the test set with high sensitivity (0.98) and precision (0.98) suggest the effectiveness of the proposed technique. Thus, it suggests the potential use of the proposed technique in other X-ray imagery-based infectious disease analysis.


Assuntos
COVID-19 , Aprendizado Profundo , Fotoquimioterapia , Algoritmos , Humanos , Redes Neurais de Computação , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Radiografia Torácica , SARS-CoV-2 , Raios X
11.
Photodiagnosis Photodyn Ther ; 35: 102474, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34358708

RESUMO

Keratoacanthoma (KA)-like squamous cell carcinoma (SCC) is inclined to be diagnosed as KA due to its resemblance to KA in appearance. A giant facial KA-like SCC has aggressive growth and malignant metastasis, and seriously affects health and aesthetics. Prompt and appropriate treatment is extremely crucial and is a great challenge. Herein, we report a case of surgery combined with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the successful management of a giant KA-like SCC in the left eyebrow of an elderly woman, providing reference for more efficient disposal of such cases in clinic.


Assuntos
Carcinoma de Células Escamosas , Ceratoacantoma , Fotoquimioterapia , Neoplasias Cutâneas , Idoso , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/cirurgia , Sobrancelhas , Feminino , Humanos , Ceratoacantoma/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico
12.
Photodiagnosis Photodyn Ther ; 35: 102476, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34358709

RESUMO

BACKGROUND: Thermal photodynamic disinfection procedures have been proposed for adjunctive endodontic treatment. This study assessed photothermal disinfection relative to root dentin temperature and the thermal effects of simulated periodontal blood flow. METHODS: Thirty freshly extracted human single-rooted teeth were prepared endodontically using a 45/.02 master apical file. The root surfaces were coated with wax and covered with thermoforming sheets, leaving a circumferential space of 0.25 mm after wax removal. The sheets were perforated to allow fluid circulation through the simulated periodontal space. Irradiation was performed in two groups of 30: I, 810 nm laser (1.5 W, continuous wave), 4 × 5 s; II, photothermal group: indocyanine green and 810 nm laser (200 mW, continuous wave), 20 s. Thermographic measurements were performed at different water flow rates (6, 2.6, 0 mL/min) with a baseline temperature of 37 °C. Nonparametric statistical analysis was performed (Wilcoxon). RESULTS: The highest temperature change (median 7.52 °C, range 0.82-18.32 °C) was with 810 nm laser irradiation in group I, without any simulated blood flow. Fluid circulation resulted in a significant reduction in temperature changes in this group (median 2.14 °C, range 0.37-9.83 °C; p  < 0.05). The lowest temperature changes were in the photothermal group with a water flow rate of 6 mL/min (median 0.79 °C, range 0.00-3.88 °C; p < 0.05). CONCLUSION: Photothermal disinfection of root canals can increase root canal dentin temperatures, but periodontal fluid circulation has a cooling effect on the outer root surface, reducing the risk of potential thermal injury to periodontal tissue.


Assuntos
Desinfecção , Fotoquimioterapia , Cavidade Pulpar , Dentina , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Preparo de Canal Radicular , Temperatura
13.
Photodiagnosis Photodyn Ther ; 35: 102475, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34358710

RESUMO

BACKGROUND: The aim of this study was to evaluate potential changes in choroidal flow in patients with newly diagnosed obsessive-compulsive disorder based on optical coherence tomography angiography findings and to investigate the relationship between subfoveal choroidal thickness and choriocapillaris flow area. METHODS: This prospective study included newly diagnosed obsessive-compulsive disorder patients and healthy controls. All patients underwent enhanced depth imaging-optical coherence tomography imaging to assess the subfoveal choroidal thickness and optical coherence tomography angiography imaging to evaluate the choriocapillaris flow area. RESULTS: A total of 55 patients with obsessive-compulsive disorder and 50 controls were included. The mean subfoveal choroidal thickness was significantly greater in the obsessive-compulsive disorder group compared to the control group (p˂0.001). Regarding the choriocapillaris flow area, the values for area with a radius of 1 mm, 2 mm and 3 mm were significantly lower in the obsessive-compulsive disorder group than in the control group (p=0.019, p=0.014, and p=0.004, respectively). There was a significant negative correlation between subfoveal choroidal thickness and choriocapillaris flow area with a radius of 1mm (r=-0.387, p=0.024). CONCLUSION: Choroidal changes in obsessive-compulsive disorder patients suggest the choroidal features of uncomplicated pachychoroid. Obsessive-compulsive disorder may be prone to a spectrum of conditions characterized by pachychoroid features.


Assuntos
Coriorretinopatia Serosa Central , Transtorno Obsessivo-Compulsivo , Fotoquimioterapia , Corioide/diagnóstico por imagem , Angiofluoresceinografia , Humanos , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Estudos Prospectivos , Estudos Retrospectivos , Tomografia de Coerência Óptica
14.
Photodiagnosis Photodyn Ther ; 35: 102490, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34419676

RESUMO

OBJECTIVE: To evaluate the value of Wood's lamp examination combined with 5-aminolevulinic acid (5-ALA) photodynamic therapy (PDT) to determine positive tumor margins in patients with extramammary Paget's disease (EMPD) before surgery. METHODS: We admitted 36 patients with EMPD from January 2016 to June 2019. The experimental group was the 5-ALA-PDT group, and the control group was the wide local excision (WLE) group. In the 5-ALA-PDT group, Wood's lamp examination combined with 5-ALA-PDT was used to trace the fluorescence range, and multipoint biopsy was performed according to the pathology to determine the final excision scope. We applied the standard partial expansion excision method for the WLE group, while frozen pathology assessment was applied to confirm the excision range. We measured the overall resection area of the WLE group and 5-ALA-PDT group. We analyzed the overall duration of surgery, the number of frozen pathology sections, patient satisfaction with appearance and function, the rate of functional sequelae, and the recurrence rate for both groups. RESULTS: The results suggested that the difference in final resection margin between the WLE group and the 5-ALA-PDT group was significant. The number of frozen pathology sections, overall surgery time, and recurrence rate were significantly lower in the experimental group than in the control group (p<0.05). The occurrence rate of functional sequelae in the experimental group was lower, and patient satisfaction with appearance and function was significantly higher than that of the control group (p<0.05). CONCLUSION: Wood's lamp examination combined with 5-ALA-PDT may predict tumor margins in EMPD.


Assuntos
Doença de Paget Extramamária , Fotoquimioterapia , Ácido Aminolevulínico/uso terapêutico , Humanos , Margens de Excisão , Recidiva Local de Neoplasia/tratamento farmacológico , Doença de Paget Extramamária/tratamento farmacológico , Doença de Paget Extramamária/cirurgia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico
15.
Molecules ; 26(12)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205347

RESUMO

PURPOSE: Vascular targeted photodynamic therapy (VTP) is a nonsurgical tumor ablation approach used to treat early-stage prostate cancer and may also be effective for upper tract urothelial cancer (UTUC) based on preclinical data. Toward increasing response rates to VTP, we evaluated its efficacy in combination with concurrent PD-1 inhibitor/OX40 agonist immunotherapy in a urothelial tumor-bearing model. EXPERIMENTAL DESIGN: In mice allografted with MB-49 UTUC cells, we compared the effects of combined VTP with PD-1 inhibitor/OX40 agonist with those of the component treatments on tumor growth, survival, lung metastasis, and antitumor immune responses. RESULTS: The combination of VTP with both PD-1 inhibitor and OX40 agonist inhibited tumor growth and prolonged survival to a greater degree than VTP with either immunotherapeutic individually. These effects result from increased tumor infiltration and intratumoral proliferation of cytotoxic and helper T cells, depletion of Treg cells, and suppression of myeloid-derived suppressor cells. CONCLUSIONS: Our findings suggest that VTP synergizes with PD-1 blockade and OX40 agonist to promote strong antitumor immune responses, yielding therapeutic efficacy in an animal model of urothelial cancer.


Assuntos
Receptor de Morte Celular Programada 1/agonistas , Receptores OX40/agonistas , Neoplasias Urológicas/imunologia , Neoplasias Urológicas/terapia , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Imunidade/efeitos dos fármacos , Imunoterapia/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fotoquimioterapia/métodos , Linfócitos T/efeitos dos fármacos , Neoplasias Urológicas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
16.
Commun Biol ; 4(1): 803, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34211094

RESUMO

Polyamine detection and depletion have been extensively investigated for cancer prevention and treatment. However, the therapeutic efficacy is far from satisfactory, mainly due to a polyamine compensation mechanism from the systemic circulation in the tumor environment. Herein, we explore a new solution for improving polyamine detection as well as a possible consumption therapy based on a new photosensitizer that can efficiently consume polyamines via an irreversible chemical reaction. The new photosensitizer is pyrrolopyrroleaza-BODIPY pyridinium salt (PPAB-PyS) nanoparticles that can react with the over-expressed polyamine in cancer cells and produce two photosensitizers with enhanced phototoxicity on cancer destruction. Meanwhile, PPAB-PyS nanoparticles provide a simultaneous ratiometric fluorescence imaging of intracellular polyamine. This combination polyamine consumption with a chemical reaction provides a new modality to enable polyamine detection along with photodynamic therapy as well as a putative depletion of polyamines for cancer treatment and prevention.


Assuntos
Poliaminas Biogênicas/análise , Nanopartículas/química , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Poliaminas Biogênicas/química , Linhagem Celular Tumoral , Humanos , Neoplasias/química , Neoplasias/prevenção & controle , Imagem Óptica
17.
Molecules ; 26(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200763

RESUMO

The development of new antimicrobial strategies that act more efficiently than traditional antibiotics is becoming a necessity to combat multidrug-resistant pathogens. Here we report the efficacy of laser-light-irradiated 5,10,15,20-tetrakis(m-hydroxyphenyl)porphyrin (mTHPP) loaded onto an ethylcellulose (EC)/chitosan (Chs) nanocomposite in eradicating multi-drug resistant Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans. Surface loading of the ethylcelllose/chitosan composite with mTHPP was carried out and the resulting nanocomposite was fully characterized. The results indicate that the prepared nanocomposite incorporates mTHPP inside, and that the composite acquired an overall positive charge. The incorporation of mTHPP into the nanocomposite enhanced the photo- and thermal stability. Different laser wavelengths (458; 476; 488; 515; 635 nm), powers (5-70 mW), and exposure times (15-45 min) were investigated in the antimicrobial photodynamic therapy (aPDT) experiments, with the best inhibition observed using 635 nm with the mTHPP EC/Chs nanocomposite for C. albicans (59 ± 0.21%), P. aeruginosa (71.7 ± 1.72%), and S. aureus (74.2 ± 1.26%) with illumination of only 15 min. Utilization of higher doses (70 mW) for longer periods achieved more eradication of microbial growth.


Assuntos
Antibacterianos/química , Celulose/análogos & derivados , Quitosana/química , Nanocompostos/química , Porfirinas/química , Piridonas/química , Pirróis/química , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Linhagem Celular , Celulose/química , Chlorocebus aethiops , Lasers , Luz , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Células Vero
18.
Chem Commun (Camb) ; 57(59): 7296-7299, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34223569

RESUMO

A chlorine e6 (Ce6) and curcumin (Cur) based self-delivery nanomedicine (CeCu) is prepared for chemotherapy sensitized photodynamic therapy (PDT). The chemotherapeutic agent of Cur could inhibit the TrxR activity to destroy the cellular ROS-defence system for enhanced PDT, which provides synergistic effects for tumor precision therapy in consideration of the unfavorable tumor microenvironments.


Assuntos
Nanomedicina , Fotoquimioterapia/métodos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Curcumina/metabolismo , Curcumina/farmacologia , Humanos , Camundongos , Microscopia Confocal , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/química , Porfirinas/metabolismo , Porfirinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Tiorredoxina Dissulfeto Redutase/metabolismo , Transplante Heterólogo , Microambiente Tumoral
19.
J Photochem Photobiol B ; 222: 112274, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34330082

RESUMO

Photodynamic therapy (PDT) has gained much attention in tumor therapy because of its special advantages. PDT heavily depends on the oxygen, yet the tumor microenvironment (TME) is a hypoxic and acid milieu, which weakens the PDT effect. Based on the consideration that the TME deteriorated by the PDT oxygen consumption could activate the hypoxic-sensitive small-molecule drug, we designed and prepared an integrated nanocomposite including zirconium ion metal organic framework (carrier), pyropheophorbide-a (PPa, photosensitizer), and 6-amino flavone (AF, hypoxic-sensitive drug), aiming to exert a cascaded PDT-chemotherapy (CT) antitumor effect and to solve the hypoxic challenge. The prepared nanocomposite showed great stability under the physiological (pH 7.4) condition and could continuously release PPa and AF under slightly acidic pH condition (pH 6.4), suggesting a tumor microenvironment responsive feature. Systematical in vitro and in vivo researches under various conditions (light, dark, hypoxic and normoxic) have showed that the obtained Zr-MOF@PPa/AF@PEG nanoparticles (NPs) had good biocompatibility and could achieve efficient antitumor effects based on PDT- chemotherapy (CT) cascade process. Finally, bright red fluorescence was observed in the tumor cells after internalization implying an application potential in tumor imaging.


Assuntos
Clorofila/análogos & derivados , Flavonoides/química , Estruturas Metalorgânicas/química , Nanocompostos/química , Fotoquimioterapia/métodos , Nanomedicina Teranóstica , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Clorofila/química , Clorofila/metabolismo , Clorofila/uso terapêutico , Liberação Controlada de Fármacos , Feminino , Flavonoides/metabolismo , Flavonoides/uso terapêutico , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Nanocompostos/uso terapêutico , Nanocompostos/toxicidade , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Polietilenoglicóis/química , Oxigênio Singlete/metabolismo , Microambiente Tumoral , Zircônio/química
20.
Photodiagnosis Photodyn Ther ; 35: 102420, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34242818

RESUMO

BACKGROUND: Accurate diagnosis of peritoneal metastasis in gastric cancer (GC) is important to determine the appropriate treatment. This study aimed to examine whether matrix metalloprotease-14 (MMP-14) was a candidate enzyme in fluorescence imaging for the diagnosis of peritoneal metastasis in GC. METHODS: GC and normal peritoneal (NP) tissues from 96 and 20 patients, respectively were evaluated for MMP-14 expression. Live cell imaging of GC cell lines (NUGC4, MKN45, MKN74, HGC-27, and Kato-III) was performed using the MMP-14-activatable fluorescence probe; BODIPY-MMP. Furthermore, the overall survival (OS) was calculated in all patients (n = 96). RESULTS: MMP-14 expression was significantly higher in GC tissues (median: 3.57 ng/mg protein; range:0.64-24.4 ng/mg protein) than in NP tissues (median: 1.34 ng/mg protein; median: 0.53-3.09 ng/mg protein) (P < 0.01). Receiver operating characteristic curves showed that the area under the curve, sensitivity, and specificity were 0.907, 84.4%, and 90.0%, respectively. In live cell imaging using the BODIPY-MMP, fluorescence was observed in five GC cell lines. In the analysis of OS, the high expression of the MMP-14 group had a significantly poorer OS rate than the low expression of the MMP-14 group (P = 0.02). In the multivariate analyses, MMP-14 expression was an independent risk factor for OS (hazard ratio: 2.33; 95 % confidence interval: 1.05-5.45; P = 0.04). CONCLUSION: MMP-14 is a promising enzyme in intraoperative fluorescence imaging for peritoneal metastasis in GC, especially in patients with poor prognosis.


Assuntos
Neoplasias Peritoneais , Fotoquimioterapia , Neoplasias Gástricas , Biomarcadores Tumorais , Humanos , Metaloproteinase 14 da Matriz , Neoplasias Peritoneais/diagnóstico por imagem , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Prognóstico , Neoplasias Gástricas/diagnóstico por imagem
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