Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 17.829
Filtrar
1.
Medicine (Baltimore) ; 98(39): e17355, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574879

RESUMO

BACKGROUND: Molar incisor hypomineralization (MIH) is a change in the formation of dental enamel of systemic origin that affects at least one of the first 4 permanent molars and usually affects incisors. During the eruption, the affected surfaces tend to fracture, exposing the dentin, which causes excessive sensitivity in addition to making the region very susceptible to the appearance of carious lesions. The objective of this research will be to evaluate the clinical effect of antimicrobial photodynamic therapy (aPDT) in permanent teeth with severe and sensitive MIH. METHODS: The methodology will be based on the selection of patients from 6 to 12 years of age with permanent molar teeth, randomly divided in 2 groups. The selected teeth should have MIH on the occlusal surface, indicated for clinical restorative treatment. In Group 1, aPDT will be applied for the treatment of infected dentin. Afterward, the teeth will be restored with high viscosity glass ionomer cement. In Group 2, the removal of the softened dentin around the side walls of the cavity with sharp dentine curettes and posterior restoration with high viscosity glass ionomer cement will be performed. All patients will have clinical and radiographic follow-up with a time interval of 6 and 12 months. The data obtained will be submitted to descriptive statistical analysis to evaluate the association of categorical variables. Chi-square test and Fisher exact test will be applied, to analyze the correlation between the continuous variables, Pearson correlation test will be applied. For the analysis of dentin density in the scanned radiographic images and the microbiological results for colony-forming units, ANOVA and Kruskal-Wallis will be applied. DISCUSSION: Often in the presence of severe MIH, the presence of dentin sensitivity is also associated with caries lesion, making it even more necessary to respect the principles of minimal intervention. TRIAL REGISTRATION: NCT03904641.


Assuntos
Anti-Infecciosos/uso terapêutico , Hipoplasia do Esmalte Dentário/tratamento farmacológico , Fotoquimioterapia/métodos , Criança , Hipoplasia do Esmalte Dentário/microbiologia , Dentina , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego , Resultado do Tratamento
2.
Braz Oral Res ; 33: e092, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576904

RESUMO

This study evaluated the effect of antimicrobial photodynamic therapy (aPDT) on the endodontic treatment of apical periodontitis (AP). AP was induced in 48 premolars of 6 dogs. After biomechanical preparation, the teeth were divided into 4 groups: Calcium-Hydroxide (CH)/120d and CH/180d: root canals filled with CH-based dressing for 15 days before obturation; aPDT/120d and aPDT/180d: conditioning with phenothiazine photosensitizer (10 mg/mL) for 1 minute and irradiation with diode laser in the same session as obturation. Root filling was performed with AH Plus sealer. After the experimental periods, animals were euthanized and teeth were submitted for histology. HE staining was performed for descriptive analysis of the periapical region, measurement of apical periodontitis and for inflammatory cells, and blood vessels count. Immunohistochemistry was performed for osteopontin (OPN) and alkaline phosphatase (ALP). Data were analyzed statistically by two-way ANOVA and chi-square test (α = 5%). Teeth in Group CH/120d presented only a slightly enlarged periodontal ligament (PL) with advanced repair. Group aPDT/120d presented the PL moderately enlarged, with moderate inflammatory infiltrate and few collagen fibers. The same pattern was observed at 180 days. AP lesions in CH-treated groups were smaller than those in aPDT-treated groups (p < 0.001) with more blood vessels (p < 0.0001), regardless of the evaluation period, without significant differences in the number of inflammatory cells (p > 0.05). CH-treated groups showed significantly more intense immunostaining for ALP and OPN (p < 0.001) in both periods. Although aPDT stimulated angiogenesis and expression of bone formation markers, the two-session endodontic treatment with CH-based dressing promoted better apical periodontitis repair.


Assuntos
Cimentos para Ossos/uso terapêutico , Hidróxido de Cálcio/uso terapêutico , Periodontite Periapical/tratamento farmacológico , Fotoquimioterapia/métodos , Tratamento do Canal Radicular/métodos , Animais , Vasos Sanguíneos/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Imuno-Histoquímica , Neovascularização Fisiológica/efeitos dos fármacos , Periodontite Periapical/patologia , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
3.
Medicine (Baltimore) ; 98(39): e16976, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574796

RESUMO

RATIONALE: Halitosis is an unpleasant odor that emanates from the mouth. Studies show halitosis returns in a week, after treatment with PDT. Probably, bacteria living in the periodontal sulcus could recolonize the dorsum of the tongue. Until nowadays, there are no study in adult population that associates halitosis and periodontal treatment with follow-up evaluation. The aim of this randomized, controlled, single-blinded clinical trial is to treat oral halitosis in healthy adults with photodynamic therapy (PDT), associated with periodontal treatment and follow them up for 3 months. PATIENT CONCERNS:: the concerns assessments will be done over the study using anamnesis interviews and specific questionnaire. DIAGNOSES:: halitosis will be evaluated by OralChroma. INTERVENTIONS: The participants (n = 40) with halitosis will be randomized into 2 groups: G1-treatment with PDT (n = 20) or G2-cleaning of the tongue with a tongue scraper (n = 20). OUTCOMES: Halitosis will be evaluated by measuring volatile sulfur compounds using gas chromatography. After the treatments, a second evaluation will be performed, along with a microbiological analysis (RT-PCR) for the identification of the bacteria T. denticola. The assessment of halitosis and the microbiological analysis will be repeated. After that, patients will receive periodontal treatment. The participants will return after 1 week and 3 months for an additional evaluation. Quality of life will be measured by Oral Health Impact Profile questionnaire (OHIP-14). LESSONS: This protocol will determine the effectiveness of phototherapy regarding the reduction of halitosis in adults. clinicaltrials.gov NCT03996915. ETHICS AND DISSEMINATION: This protocol received approval from the Human Research Ethics Committee of Universidade Nove de Julho (certificate number: 3.257.104). The data will be published in a peer-reviewed periodical.


Assuntos
Halitose/tratamento farmacológico , Doenças Periodontais/terapia , Fotoquimioterapia , Cromatografia Gasosa , Seguimentos , Halitose/etiologia , Halitose/microbiologia , Humanos , Pessoa de Meia-Idade , Higiene Bucal , Doenças Periodontais/complicações , Doenças Periodontais/microbiologia , Fármacos Fotossensibilizantes/uso terapêutico , Recidiva , Método Simples-Cego , Resultado do Tratamento , Treponema denticola/isolamento & purificação
4.
J Biol Regul Homeost Agents ; 33(3 Suppl. 1): 27-33, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31538447

RESUMO

Photodynamic Therapy (PDT) is a minimally invasive approach that has shown promising results in management of oral, head and neck lesions. PDT can be used alone or in combination with other conventional treatments (surgery, chemotherapy, radiotherapy). Oral Lichen Planus (OLP) is a mucosal and cutaneous chronic disease characterized by an autoimmune insult of basal keratinocytes. We aim to evaluate the feasibility of topical toluidine blue-mediated PDT for the treatment of oral cavity multifocal homogeneous white lesions by oral lichen planus without dysplastic features.


Assuntos
Líquen Plano Bucal/tratamento farmacológico , Fotoquimioterapia , Cloreto de Tolônio/uso terapêutico , Doença Crônica , Humanos , Fármacos Fotossensibilizantes
5.
Chem Commun (Camb) ; 55(72): 10792-10795, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31432816

RESUMO

Hypoxia, as an important feature in tumor sites, greatly hinders the performance of photosensitizers, thus affecting the efficacy of photodynamic therapy (PDT). Therefore, designing and preparing new photosensitizer with high photosensitivity under hypoxic condition presents a great challenge that urgently needs to be solved. In this work, a new nano-MOF material using Mn(ii) as the active center can catalytically decompose high concentrations of H2O2 in tumor cells to generate O2, thereby improving the PDT efficacy in hypoxic tumors. The Mn-MOF also produces 1O2 under light irradiation, which finally induces cancer cell apoptosis. This work offers a new strategy for the design and discovery of effective photosensitizers for PDT.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Manganês/farmacologia , Estruturas Metalorgânicas/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Hipóxia Tumoral/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Peróxido de Hidrogênio/metabolismo , Manganês/química , Estruturas Metalorgânicas/química , Camundongos , Oxigênio/metabolismo , Tamanho da Partícula , Fármacos Fotossensibilizantes/química , Propriedades de Superfície
6.
Chem Commun (Camb) ; 55(67): 9971-9974, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31367709

RESUMO

Photodynamic therapy (PDT) is a clinically approved cancer treatment that uses light, oxygen and a photosensitizer to produce localized reactive oxygen species (ROS). Due to the short lifetime of ROS, the location of the photosensitizer in the cell is believed to be the key determinant governing the outcome of PDT. To explore the effect of direct association between a photosensitizer and DNA a well know DNA-binding dye, DAPI, was converted into a photosensitizer. Br-DAPI - unlike native DAPI - upon irradiation produces ROS. We demonstrate that the ROS are only effective in inducing dsDNA breaks when Br-DAPI is bound to DNA. In cancer cells (A549) Br-DAPI causes rapid light dependent cell death. This work supports the design of photosensitizers which bind with high affinity to the DNA of target cells for potentially more effective PDT.


Assuntos
Bromo/química , DNA/química , Indóis/química , Fármacos Fotossensibilizantes/química , Células A549 , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Dano ao DNA , Corantes Fluorescentes/química , Humanos , Luz , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Estudo de Prova de Conceito , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo
7.
Inorg Chem ; 58(16): 10778-10790, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31386351

RESUMO

A new family of cyclometalated ruthenium(II) complexes [Ru(N^N)2(C^N)]+ derived from the π-extended benzo[h]imidazo[4,5-f]quinolone ligand appended with thienyl groups (n = 1-4, compounds 1-4) was prepared and its members were characterized for their chemical, photophysical, and photobiological properties. The lipophilicities of 1-4, determined as octanol-water partition coefficients (log Po/w), were positive and increased with the number of thienyl units. The absorption and emission bands of the C^N compounds were red-shifted by up to 200 nm relative to the analogous Ru(II) diimine systems. All of the complexes exhibited dual emission with the intraligand fluorescence (1IL, C^N-based) shifting to lower energies with increasing n and the metal-to-ligand charge transfer phosphorescence (3MLCT, N^N-based) remaining unchanged. Compounds 1-3 exhibited excited state absorption (ESA) profiles consistent with lowest-lying 3MLCT states when probed by nanosecond transient absorption (TA) spectroscopy with 532 nm excitation and had contributions from 1IL(C^N) states with 355 nm excitation. These assignments were supported by the lifetimes observed (<10 ns for the 1IL states and around 20 ns for the 3MLCT states) as well as a noticeable ESA for 3 with 355 nm excitation that did not occur with 532 nm excitation. Compound 4 was the only member of the family with two 3MLCT emissive lifetimes (15, 110 ns), and the TA spectra collected with both 355 and 532 nm excitation was assigned to the 3IL state, which was corroborated by its 4-6 µs lifetime. The ESA for 4 had a rise time of approximately 10 ns and an initial decay of 110 ns, which suggests a possible 3MLCT-3IL excited state equilibrium that results in delayed emission from the 3MLCT state. Compound 4 was nontoxic toward human skin melanoma cells (SKMEL28) in the dark (EC50 = >300 µM); 1-3 were cytotoxic and yielded EC50 values between 1 and 20 µM. The photocytotoxicites with visible light ranged from 87 nM with a phototherapeutic index (PI) of 13 for 1 to approximately 1 µM (PI = >267) for 4. With red light, EC50 values varied from 270 nM (PI = 21) for 3 to 12 µM for 4 (PI = >25). The larger PIs for 4, especially with visible light, were attributed to the much lower dark cytotoxicity for this compound. Because the dark cytotoxicity contributes substantially to the observed photocytotoxicity for 1-3, it was not possible to assess whether the 3IL state of 4 led to a much more potent phototoxic mechanism in the absence of dark toxicity. There was no stark contrast in cellular uptake and accumulation by laser scanning confocal and differential interference contrast microscopy to explain the large differences in dark toxicities between 1-3 and 4. Nevertheless, the study highlights a new family of Ru(II) C^N complexes where π-conjugation beyond a certain point results in low dark cytotoxicity with high photocytotoxicity, opposing the notion that cyclometalated Ru(II) systems are too toxic to be phototherapeutic agents.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Quinolonas/farmacologia , Rutênio/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligantes , Luz , Estrutura Molecular , Processos Fotoquímicos , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Quinolonas/química , Rutênio/química
8.
J Biomed Nanotechnol ; 15(10): 2045-2058, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31462370

RESUMO

Combining photodynamic therapy (PDT) and chemotherapy can improve anti-cancer efficacy. In this study, a novel copolymer PTPP combining thioketal and protoporphyrin was synthesized and tested for antitumor activity. Self-assembled PTPP micelles loaded with doxorubicin (DOX) showed uniform size, narrow particle size distribution and greater antitumor activity in vivo and in vivo than DOX-loaded micelles made from the commonly used material mPEG-PCL. Under laser irradiation, the photosensitizing protoporphyrin of DOX/PTPP produces abundant reactive oxygen species (ROS) that directly kill tumor cells as well as destroy the micelles themselves, leading to drug release. The ROS and DOX then act synergistically against the tumors. These ROS-responsive, laser-sensitive polymeric micelles may be useful for combining PDT and chemotherapy.


Assuntos
Espécies Reativas de Oxigênio/química , Doxorrubicina , Liberação Controlada de Fármacos , Micelas , Fotoquimioterapia , Polímeros
9.
Chem Commun (Camb) ; 55(69): 10226-10229, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31380870

RESUMO

A formulation of self-assembled peptido-nanomicelles has been developed for a combinational treatment of SDT, PDT and chemotherapy to nasopharyngeal carcinoma. In vitro cellular tests and in vivo mice therapy proved effective for targeted tumor growth inhibition. These merits provided a novel approach to non-invasive cancer treatments.


Assuntos
Corantes Fluorescentes/uso terapêutico , Carcinoma Nasofaríngeo/terapia , Peptídeos/uso terapêutico , Rosa Bengala/uso terapêutico , Animais , Linhagem Celular Tumoral , Terapia Combinada/métodos , Corantes Fluorescentes/administração & dosagem , Humanos , Camundongos Nus , Micelas , Carcinoma Nasofaríngeo/patologia , Peptídeos/administração & dosagem , Fotoquimioterapia/métodos , Rosa Bengala/administração & dosagem , Terapia por Ultrassom/métodos
10.
Chem Commun (Camb) ; 55(70): 10472-10475, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31411208

RESUMO

A mitochondria-targeted photodynamic therapy (PDT) agent was designed and synthesized. Upon light irradiation, it can produce photoacid and its photolysis products can further sensitize 1O2 generation, causing dual-mode (oxygen-independent and oxygen-dependent) photodynamic damage in mitochondria and killing cancer cells effectively even under hypoxic conditions.


Assuntos
Irídio/farmacologia , Mitocôndrias/metabolismo , Fotoquimioterapia , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Humanos , Espectroscopia de Prótons por Ressonância Magnética , Oxigênio Singlete/metabolismo
11.
Anticancer Res ; 39(8): 4199-4206, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366506

RESUMO

BACKGROUND/AIM: We previously synthesized a glucose-conjugated chlorin compound e6 (G-chlorin e6), and reported that it has very strong antitumor effects. The aim of the present study was to synthesize acetylated glucose-conjugated chlorin (AcN003HP) and evaluate its antitumor effect and excretion. MATERIALS AND METHODS: To evaluate the antitumor effect of AcN003HP, its IC50 was calculated as well as its accumulation in cancer cells was examined by flow cytometry. Confocal microscopy was used to observe the intracellular localization of AcN003HP. The excretion and antitumor effects of AcN003HP were also evaluated in vivo. RESULTS: AcN003HP showed stronger antitumor effects and accumulation into cancer cells compared to talaporfin sodium, a conventional photosensitizer. AcN003HP was localized in the endoplasmic reticulum. In a xenograft tumor mouse model, AcN003HP showed longer excretion time from the body than G-chlorin e6, and photodynamic therapy using AcN003HP showed very strong antitumor effects. CONCLUSION: The safety, improved controllability, and robust antitumor effects suggest AcN003HP as a good next-generation photosensitizer.


Assuntos
Neoplasias Gastrointestinais/terapia , Glucose/administração & dosagem , Fotoquimioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Acetilação/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Retículo Endoplasmático/efeitos dos fármacos , Citometria de Fluxo , Neoplasias Gastrointestinais/patologia , Glucose/síntese química , Glucose/química , Humanos , Camundongos , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Porfirinas/administração & dosagem , Porfirinas/síntese química , Porfirinas/química , Ensaios Antitumorais Modelo de Xenoenxerto
12.
J Chem Theory Comput ; 15(9): 5046-5057, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31390517

RESUMO

Halogenated BODIPY derivatives are emerging as important candidates for photodynamic therapy of cancer cells due to their high triplet quantum yield. We probed fundamental photophysical properties and interactions with biological environments of such photosensitizers. To this end, we employed static TD-DFT quantum chemical calculations as well as TD-DFT surface hopping molecular dynamics on potential energy surfaces resulting from the eigenstates of the total electronic Hamiltonian including the spin-orbit (SO) coupling. Matrix elements of an effective one-electron spin-orbit Hamiltonian between singlet and triplet configuration interaction singles (CIS) auxiliary wave functions are calculated using a new code capable of dealing with singlets and both restricted and unrestricted triplets built up from up to three different and independent sets of (singlet, alpha, and beta) molecular orbitals. The interaction with a biological environment was addressed by using classical molecular dynamics (MD) in a scheme that implicitly accounts for electronically excited states. For the surface hopping trajectories, an accelerated MD approach was used, in which the SO couplings are scaled up, to make the calculations computationally feasible, and the lifetimes are extrapolated back to unscaled SO couplings. The lifetime of the first excited singlet state estimated by semiclassical surface hopping simulations is 139 ± 75 ps. Classical MD demonstrates that halogenated BODIPY in the ground state, in contrast to the unsubstituted one, is stable in the headgroup region of minimalistic cell membrane models, and while in the triplet state, the molecule relocates to the membrane interior ready for further steps of photodynamic therapy.


Assuntos
Compostos de Boro/química , Simulação de Dinâmica Molecular , Fotoquimioterapia , Teoria da Densidade Funcional , Processos Fotoquímicos , Fármacos Fotossensibilizantes/química , Teoria Quântica , Propriedades de Superfície
13.
Int J Nanomedicine ; 14: 4931-4947, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371941

RESUMO

Background: Phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), is a promising noninvasive strategy in the treatment of cancers due to its highly localized specificity to tumors and minimal side effects to normal tissues. However, single phototherapy often causes tumor recurrence which hinders its clinical applications. Therefore, developing a NIR-guided dendritic nanoplatform for improving the phototherapy effect and reducing the recurrence of tumors by synergistic chemotherapy and phototherapy is essential. Methods: A fluorescent targeting ligand, insisting of ICG derivative cypate and a tumor penetration peptide iRGD (CRGDKGPDC), was covalently combined with PAMAM dendrimer to prepare a single agent-based dendritic theranostic nanoplatform iRGD-cypate-PAMAM-DTX (RCPD). Results: Compared with free cypate, the resulted RCPD could generate enhanced singlet oxygen species while maintaining its fluorescence intensity and heat generation ability when subjected to NIR irradiation. Furthermore, our in vitro and in vivo therapeutic studies demonstrated that compared with phototherapy or chemotherapy alone, the combinatorial chemo-photo treatment of RCPD with the local exposure of NIR light can significantly improve anti-tumor efficiency and reduce the risk of recurrence of tumors. Conclusion: The multifunctional theranostic platform (RCPD) could be used as a promising method for NIR fluorescence image-guided combinatorial treatment of tumor cancers.


Assuntos
Antineoplásicos/farmacologia , Dendrímeros/química , Raios Infravermelhos , Nanopartículas/química , Fototerapia , Animais , Proliferação de Células/efeitos dos fármacos , Terapia Combinada , Docetaxel/farmacologia , Endocitose/efeitos dos fármacos , Fluorescência , Células Hep G2 , Temperatura Alta , Humanos , Indóis/farmacologia , Camundongos Nus , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Oligopeptídeos/química , Fotoquimioterapia , Propionatos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica
14.
Int J Nanomedicine ; 14: 5073-5085, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371948

RESUMO

Purpose: To potentiate the anticancer activity of curcumin (CUR) by improving its cell penetration potentials through formulating it into nanostructured lipid carriers (NLCs) and using the prepared NLCs in photodynamic therapy. Methods: A 3×4 factorial design was used to obtain 12 CUR-NLCs using two factors on different levels: (1) the solid lipid type at four levels and (2) the solid to liquid lipid ratio at three levels. Olive oil, Tween 80 and lecithin were chosen as liquid lipid, surfactant and co-surfactant, respectively. CUR-NLCs prepared by high shear hot homogenization method were evaluated by determination of particle size (PS), polydispersity index, zeta potential (ZP), entrapment efficiency percent, drug loading percent and in vitro drug release. Optimization was based on the evaluation results using response surface modeling (RSM). Optimized formulae were tested for their in vitro release pattern and for dark and photo-cytotoxic anticancer activity on breast cancer cell line in comparison to free CUR. Results: Evaluation tests showed the appropriateness of NLCs prepared from glyceryl monooleate and Geleol™ helped choosing two optimized formulae, PE3 and GE3. PE3 (prepared using glyceryl monooleate) showed enhanced release rates compared to GE3 (prepared from Geleol) and superior cytotoxic anticancer activity compared to both GE3 and free CUR under both light and dark conditions. The small mean PS, spherical shape as well as the negative ZP enhanced the internalization of the NLCs within cells. Modulation and inhibition of P-glycoprotein expression by glyceryl monooleate synergized the cytotoxic activity of CUR. Conclusion: CUR loading in NLCs enhanced its cell penetration and cytotoxic anticancer properties both in dark and in light conditions.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Curcumina/uso terapêutico , Portadores de Fármacos/química , Lipídeos/química , Nanoestruturas/química , Ácidos Oleicos/química , Azeite de Oliva/química , Fotoquimioterapia , Sobrevivência Celular/efeitos dos fármacos , Curcumina/farmacologia , Liberação Controlada de Fármacos , Feminino , Humanos , Células MCF-7 , Nanoestruturas/ultraestrutura , Tamanho da Partícula , Eletricidade Estática
15.
J Biomed Nanotechnol ; 15(9): 1867-1880, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31387675

RESUMO

The present study aims to evaluate the effect of the ethyl acetate extract of Cichorium (EAEC) as a novel photosensitizer in photodynamic therapy (PDT) of colorectal carcinoma (CRC) HCT116 and SW620 cells. The absorption and fluorescence spectra of EAEC were measured using a UV-vis spectrophotometer and fluorescence spectrophotometer, respectively. EAEC-induced reactive oxygen species (ROS) production in HCT116 and SW620 cells was detected using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and glutathione/glutathione disulfide (GSH/GSSG). The photo- and dark toxicities of EAEC were estimated using the Cell Counting Kit-8 (CCK-8) assay. Cellular uptake and localization of EAEC were detected by confocal laser fluorescence microscopy. Annexin V-FITC/PI staining, Western blotting and immunofluorescence staining were used to assess apoptosis and autophagy. The antitumor activity of EAEC was confirmed in a xenograft model. Finally, effects on the PERK pathway were verified using qRT-PCR and Western blotting. EAEC displayed absorption and fluorescence emission peaks at 660 nm and 678 nm, respectively. EAEC induced ROS production in CRC cells. Assessment of dark toxicity showed that treatment with EAEC alone induced little cytotoxicity in CRC or normal cells but that EAEC-PDT induced significant photocytotoxicity in CRC cells in a time- and dose-dependent manner. After cellular uptake, EAEC was located in the mitochondria. Treatment with EAEC-PDT reduced xenograft tumor size. Further evaluation suggested that activation of the PERK pathway mediates these effects, as the apoptotic rate and autophagy flux increased markedly after EAEC-PDT. EAEC, a natural photosensitizer extracted from Cichorium, displays potential utility in PDT of CRC by targeting the PERK pathway.


Assuntos
Autofagia , Neoplasias Colorretais , Fotoquimioterapia , Acetatos , Apoptose , Linhagem Celular , Linhagem Celular Tumoral , Estresse do Retículo Endoplasmático , Humanos , Fármacos Fotossensibilizantes , Proteínas Quinases , Espécies Reativas de Oxigênio
16.
Oncology ; 97(4): 191-201, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31266042

RESUMO

Endoscopic decompression of bile duct stenosis in unresectable cholangiocarcinoma (CC) may be difficult due to localization of the tumor, but it is important for pursuing oncologic treatment afterwards. Besides the initial diagnosis, jaundice and cholangitis are the most important indications for immediate endoscopic treatment. Endoscopic retrograde cholangiopancreatography is the favored approach for biliary access and stent placement. Hilar tumors are more difficult to treat and sometimes need higher endoscopic or radiologic expertise. In general, biliary decompression is accompanied by antibiotic treatment. Oncologic treatment of CC remains difficult, as it has to be interrupted when -infectious complications occur. For chemotherapy, a gemcitabine/cisplatin-based regime is favored. A validated -second-line treatment does not exist. Several therapeutic options are therefore offered to patients, including photodynamic therapy, selective internal radiotherapy, and high-dose radiotherapy. Exact treatment recommendations do not exist due to tumor rarity and lack of randomized controlled trials. In the present article, we take a look at current endoscopic, medical, and oncologic challenges from the endoscopist's point of view.


Assuntos
Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/terapia , Endoscopia , Oncologia/tendências , Antibacterianos/uso terapêutico , Antineoplásicos/farmacologia , Colangiopancreatografia Retrógrada Endoscópica , Colangite/terapia , Constrição Patológica , Humanos , Fotoquimioterapia , Radioterapia
17.
Biomater Sci ; 7(9): 3855-3865, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31305807

RESUMO

Fluorogens with aggregation-induced emission (AIE) characteristics (AIEgens) possess unique optical properties, design flexibility, and multi-functional capabilities and have established their niche as smart materials since their discovery in 2001. In recent years, AIEgens have found varied applications in sensing, imaging, and therapy in biomedical research. In this work, we systematically and comprehensively investigate the in vitro anticancer activity of AIEgens. We report the high cytotoxicity of AIEgens against cancer cells, especially against cancer stem cells (CSCs) which show high resistance to existing therapeutic drug regimens. Furthermore, we explore the role of AIEgens as novel image-guided chemotherapy agents that offer a new avenue for efficient cancer treatment.


Assuntos
Antineoplásicos/química , Corantes Fluorescentes/química , Fármacos Fotossensibilizantes/química , Estilbenos/química , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Corantes Fluorescentes/farmacologia , Hemólise , Humanos , Invasividade Neoplásica , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Imagem Óptica/métodos , Fotoquimioterapia , Estilbenos/farmacologia , Nanomedicina Teranóstica
18.
Chem Commun (Camb) ; 55(67): 9904-9914, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31360938

RESUMO

The successful clinical application of the three generation platinum anticancer drugs, cisplatin, carboplatin and oxaliplatin, has promoted research interest in metallodrugs; however, the problems of drug resistance and adverse effects have hindered their further application and effects. Thus, scientists are searching for new anticancer metallodrugs with lower toxicity and higher efficacy. The ruthenium complexes have emerged as the most promising alternatives to platinum-based anticancer agents because of their unique multifunctional biochemical properties. In this review, we first focus on the anticancer applications of various ruthenium complexes in different signaling pathways, including the mitochondria-mediated pathway, the DNA damage-mediated pathway, and the death receptor-mediated pathway. We then discuss the functionalization and cancer-targeting designs of different ruthenium complexes in conjunction with other therapies such as photodynamic therapy, photothermal therapy, radiosensitization, targeted therapy and nanotechnology for precise cancer therapy. This review will help in designing and accelerating the research progress regarding new anticancer ruthenium complexes.


Assuntos
Antineoplásicos/química , Complexos de Coordenação/química , Rutênio/química , Animais , Antineoplásicos/uso terapêutico , Complexos de Coordenação/uso terapêutico , Descoberta de Drogas , Humanos , Estrutura Molecular , Terapia de Alvo Molecular , Nanopartículas/química , Fotoquimioterapia/métodos , Medicina de Precisão , Relação Estrutura-Atividade
19.
Anticancer Res ; 39(7): 3739-3744, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262900

RESUMO

BACKGROUND/AIM: Cancer incidence and mortalities are growing worldwide, therefore research and development of more effective and less invasive treatments, such as photodynamic therapy, are needed. Herein, we investigated the methylene blue (MB) photoactivation effects in lung epithelial cells (BEAS-2B) and lung adenocarcinoma cells (H-441). MATERIALS AND METHODS: The reactive oxygen species (ROS) produced by the laser photoactivation of MB in aqueous solutions and cell cultures were measured with probes, and the cell viability was evaluated with a colorimetric assay. RESULTS: MB up to 31.26 µM did not induce detectable effects in BEAS-2B cells. However, H-441 cells presented adverse effects below that concentration in the same range of fluencies studied. These results are in concordance with the ROS production in H-441 cells, while in BEAS-2B cells the production of ROS was less significant compared to the control. CONCLUSION: Photoactivation of MB at concentrations below 31.26 µM could be used for the selective treatment of H-441 cells over non-cancer cells.


Assuntos
Adenocarcinoma/tratamento farmacológico , Células Epiteliais/efeitos dos fármacos , Luz , Neoplasias Pulmonares/tratamento farmacológico , Azul de Metileno/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Adenocarcinoma/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Espécies Reativas de Oxigênio/metabolismo
20.
Photochem Photobiol Sci ; 18(8): 2012-2022, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31282525

RESUMO

Organic-metal complexes are promising molecules for use in photodynamic therapy (PDT). The aim of this study was to investigate in vitro effects of novel Ru(ii) and Ir(iii) BODIPY complexes for PDT. These hybrid organic-metal molecules (Ru-BD and Ir-BD) have been synthesized via reactions of a BODIPY precursor (BD) with a phenanthroline unit bearing Ru(ii) (3) and novel Ir(iii) (4) compounds. The crystal structures of the new distyryl BODIPY (BD) and Ru(ii) complex (3) are also reported. The photophysical and singlet oxygen generation properties of Ru-BD and Ir-BD were investigated in comparison with unsubstituted BODIPY (BD). Moreover, Ru-BD and Ir-BD have been biologically evaluated in vitro in chronic myeloid leukemia and cervical cancer cell lines in terms of photodynamic therapy efficacy in the presence of BD control. These complexes were not toxic in the dark but red light was needed to induce cell death. These data support the fact that Ru-BD could be accepted as a valuable photosensitizer-drug for further PDT treatment.


Assuntos
Antineoplásicos/farmacologia , Compostos de Boro/farmacologia , Corantes/farmacologia , Compostos Organometálicos/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos de Boro/síntese química , Compostos de Boro/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Corantes/síntese química , Corantes/química , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Irídio/química , Irídio/farmacologia , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Rutênio/química , Rutênio/farmacologia , Oxigênio Singlete/análise , Oxigênio Singlete/metabolismo , Células Tumorais Cultivadas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA