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1.
Nanoscale ; 13(35): 14879-14899, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34533177

RESUMO

Colorectal cancer (CRC) has a poor prognosis and urgently needs better therapeutic approaches. 5-Aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) based photodynamic therapy (PDT) is already used in the clinic for several cancers but not yet well investigated for CRC. Currently, systemic administration of ALA offers a limited degree of tumour selectivity, except for intracranial tumours, limiting its wider use in the clinic. The combination of effective ALA-PDT and chemotherapy may provide a promising alternative approach for CRC treatment. Herein, theranostic Ag2S quantum dots (AS-2MPA) optically trackable in near-infrared (NIR), conjugated with endothelial growth factor receptor (EGFR) targeting Cetuximab (Cet) and loaded with ALA for PDT monotherapy or ALA/5-fluorouracil (5FU) for the combination therapy are proposed for enhanced treatment of EGFR(+) CRC. AS-2MPA-Cet exhibited excellent targeting of the high EGFR expressing cells and showed a strong intracellular signal for NIR optical detection in a comparative study performed on SW480, HCT116, and HT29 cells, which exhibit high, medium and low EGFR expression, respectively. Targeting provided enhanced uptake of the ALA loaded nanoparticles by strong EGFR expressing cells and formation of higher levels of PpIX. Cells also differ in their efficiency to convert ALA to PpIX, and SW480 was the best, followed by HT29, while HCT116 was determined as unsuitable for ALA-PDT. The therapeutic efficacy was evaluated in 2D cell cultures and 3D spheroids of SW480 and HT29 cells using AS-2MPA with either electrostatically loaded, hydrazone or amide linked ALA to achieve different levels of pH or enzyme sensitive release. Most effective phototoxicity was observed in SW480 cells using AS-2MPA-ALA-electrostatic-Cet due to enhanced uptake of the particles, fast ALA release and effective ALA-to-PpIX conversion. Targeted delivery reduced the effective ALA concentration significantly which was further reduced with codelivery of 5FU. Delivery of ALA via covalent linkages was also effective for PDT, but required a longer incubation time for the release of ALA in therapeutic doses. Phototoxicity was correlated with high levels of reactive oxygen species (ROS) and apoptotic/necrotic cell death. Hence, both AS-2MPA-ALA-Cet based PDT and AS-2MPA-ALA-Cet-5FU based chemo/PDT combination therapy coupled with strong NIR tracking of the nanoparticles demonstrate an exceptional therapeutic effect on CRC cells and excellent potential for synergistic multistage tumour targeting therapy.


Assuntos
Neoplasias Colorretais , Fotoquimioterapia , Pontos Quânticos , Ácido Aminolevulínico/farmacologia , Linhagem Celular Tumoral , Cetuximab/farmacologia , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/tratamento farmacológico , Humanos , Imagem Óptica , Fármacos Fotossensibilizantes/farmacologia , Protoporfirinas
2.
Nanoscale ; 13(31): 13506-13518, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34477755

RESUMO

Photodynamic therapy (PDT) has evolved as an essential method for infection control, but is confronted with challenges in terms of low oxygen supply, possible toxicity during light irradiation, and nonpersistent action. Herein, to address these limitations, black phosphorus (BP) is used as a photosensitizer and decorated with Pt nanoparticles and aminobenzyl-2-pyridone (APy) moieties to obtain BP@APy-Pt. The stability of BP is improved through the capture and occupation of lone-pair electrons after reductive deposition of Pt nanoparticles and covalent conjugation of APy. Pt nanoparticles on BP@APy-Pt catalyze the decomposition of endogenous H2O2 to produce oxygen for consecutive cycles with a stable production capacity. The light exposure to BP@APy-Pt generates significantly higher 1O2 levels than those of BP/light, and the generated 1O2 is partially captured by APy moieties. The captured 1O2 during 20 min of illumination shows a constant release for 24 h in the dark. The cycled storage and release feature eliminates the toxicity of 1O2 at high levels during illumination and leads to efficient destruction of S. aureus and P. aeruginosa. Compared to the healing rates after treatment with BP/light (57.6%), BP@Pt/light (64.8%), BP@APy/light (77.8%), and BP@APy-Pt (48.5%), the skin wounds with infected S. aureus are fully healed after BP@APy-Pt/light treatment. Blood vessels and hair follicles are regenerated to resemble those of normal skin. Thus, this study expands the PDT strategy through integration with oxygen generation, 1O2 storage, and persistent release to promote bactericidal efficacy and eliminate side effects.


Assuntos
Oxigênio , Fotoquimioterapia , Homicídio , Peróxido de Hidrogênio , Fósforo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Staphylococcus aureus
3.
Anal Chim Acta ; 1178: 338847, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34482880

RESUMO

Photodynamic therapy has been generally developed and approved as a promising theranostic technique in recent years, which requires photosensitizers to bear high efficiency of reactive oxygen species production, precisely targeting ability and excellent biocompatibility. The real-time monitoring the microenvironments such as viscosity dynamic involved in mitophagy mediated by photodynamic therapy is significantly important to understand therapeutic process but barely reported. In this work, a pyridinium-functionalized triphenylamine derivative, (E)-4-(2-(4'-(diphenylamino)-[1,1'-biphenyl]-4-yl)vinyl)-1-methylpyridin-1-ium iodide (Mito-I), was exploited as photosensitizer for mitochondria-targeted photodynamic therapy and as fluorescent probe for imaging the mitochondrial viscosity dynamic during mitophagy simultaneously. The results indicated that the additional phenyl ring in Mito-I was beneficial to promote its efficiency of singlet oxygen production. The excellent capability of targeting mitochondria and singlet oxygen generation allowed Mito-I for the specifically mitochondria-targeted photodynamic therapy. Moreover, Mito-I displayed off-on fluorescence response to viscosity with high selectivity and sensitivity. The observed enhancement in fluorescence intensity of Mito-I revealed the increasingly mitochondrial viscosity during mitophagy mediated by the photodynamic therapy of Mito-I. As a result, this work presents a rare example to realize the mitochondria-targeting photodynamic therapy as well as the real-time monitoring viscosity dynamic during mitophagy, which is of great importance for the basic medical research involved in photodynamic therapy.


Assuntos
Mitofagia , Fotoquimioterapia , Mitocôndrias , Fármacos Fotossensibilizantes/farmacologia , Viscosidade
4.
Mater Sci Eng C Mater Biol Appl ; 128: 112341, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474891

RESUMO

In order to maximize the retention of the photodynamic therapy (PDT) efficacy, while avoiding the dilemma of hypoxia and high reducing substances in tumor tissue, fluoropolymers were synthesized in a simple and effective methods. Fluorous effect with good oxygen carrying capacity was endowed by the fluorine-containing section in fluoropolymers and the perfluorodecalin (PFD) together, the reaction site with GSH was provided by the disulfide bond, which enhanced PDT efficiency through the sequential "AND" logic gate design. Two kind of fluorine-containing nanocarriers (M-Ce6 and E-Ce6) were obtained by solvent evaporation or ultrasound emulsification with PFD, respectively. In vitro, both of them showed promising high ROS generation under photoirradiation. Benefiting by cavitation effects, E-Ce6 had a more significant statistical difference in cellular uptake. Furthermore, the cells incubating with E-Ce6 hardly were noticed that the hypoxia signal appeared under hypoxia, while reducing the intracellular GSH content by more than 15%. Through the sequential "AND" logic gate design, ROS production even under hypoxia and GSH conditions of E-Ce6 was also almost 1.5 times that of Ce6 under normoxia. Enhancing effect of E-Ce6 was 13.47 times and 6.85 times, while selectivity ratio reached 5.13 times and 4.81 times compared with Ce6 and M-Ce6. The two-pronged strategy showed a high potential for delivering the Ce6 to deep inside of cancer cells and killing it in the simulated tumor by PDT. These above results demonstrated the potential of E-Ce6, as oxygen self-sufficiency and GSH depletion nanocarriers for combined enhancement of photodynamic therapy.


Assuntos
Fotoquimioterapia , Porfirinas , Linhagem Celular Tumoral , Flúor , Oxigênio , Fármacos Fotossensibilizantes/farmacologia
5.
Nanoscale ; 13(31): 13473-13486, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34477752

RESUMO

BACKGROUND: Currently, limited tumor drug permeation, poor oxygen perfusion and immunosuppressive microenvironments are the most important bottlenecks that significantly reduce the efficacy of photodynamic therapy (PDT). The main cause of these major bottlenecks is the platelet activation maintained abnormal tumor vessel barriers. Thus, platelet inhibition may present a new way to most effectively enhance the efficacy of PDT. However, to the best of our knowledge, few studies have validated the effectiveness of such a way in enhancing the efficacy of PDT both in vivo and in vitro. In this study, perfluoro-N-(4-methylcyclohexyl) piperidine-loaded albumin (PMP@Alb) nanoparticles were discovered, which possess excellent platelet inhibition ability. After PMP@Alb treatment, remarkably enhanced intra-tumoral drug accumulation, oxygen perfusion and T cell infiltration could be observed owing to the disrupted tumor vessel barriers. Besides, the effect of ICG@Lip mediated PDT was significantly amplified by PMP@Alb nanoparticles. It was demonstrated that PMP@Alb could be used as a useful tool to improve the efficacy of existing PDT by disrupting tumor vessel barriers through effective platelet inhibition.


Assuntos
Nanopartículas , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Albuminas/farmacologia , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos Endogâmicos C57BL , Fármacos Fotossensibilizantes/farmacologia , Piperidinas/farmacologia , Microambiente Tumoral
6.
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
7.
J Photochem Photobiol B ; 222: 112258, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34399205

RESUMO

Photodynamic therapy (PDT) is an approved therapeutic approach and an alternative to conventional chemotherapy for the treatment of several types of cancer with the advantages of reducing the side effects and developing resistance mechanisms. Here, was evaluated the photosensitization capabilities of 5,10,15,20-tetrakis[4-(pyridinium-1-yl-methyl)phenyl]porphyrin (3), its N-confused isomer (4) and of the neutral precursors (1) and (2) and the results were compared with the ones obtained with the cationic 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP). Both regular porphyrin derivatives 1 and 3 showed higher efficiency to generate singlet oxygen than TMPyP. The PDT assays towards MCF-7 cells under red light irradiation (λ > 640 nm, 23.7 mW cm-2) demonstrated that the cationic porphyrin 3 is an efficient photosensitizer to kill MCF-7 breast cancer cells. The study of the cell death mechanisms induced by the photodynamic process showed that the studied porphyrin 3 and TMPyP caused cell death by autophagic flux and necrosis.


Assuntos
Apoptose/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Apoptose/efeitos da radiação , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Feminino , Humanos , Luz , Células MCF-7 , Microscopia Confocal , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/química , Porfirinas/uso terapêutico , Oxigênio Singlete/metabolismo
8.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34445089

RESUMO

Apical periodontitis, an inflammatory lesion causing bone resorption around the apex of teeth, is treated by eradicating infectious bacteria from the root canal. However, it has a high recurrence rate and often requires retreatment. We investigated the bactericidal effect of antimicrobial photodynamic therapy (aPDT)/photodynamic antimicrobial chemotherapy (PACT) using indocyanine green (ICG)-loaded nanospheres coated with chitosan and a diode laser on a biofilm of Enterococcus faecalis, a pathogen of refractory apical periodontitis. Biofilm of E. faecalis was cultured in a porcine infected root canal model. ICG solution was injected into the root canal, which was then irradiated with a laser (810 nm wavelength) from outside the root canal. The bactericidal effect was evaluated by colony counts and scanning electron microscopy. The result of the colony counts showed a maximum 1.89 log reduction after irradiation at 2.1 W for 5 min. The temperature rise during aPDT/PACT was confirmed to be within a safe range. Furthermore, the light energy transmittance through the root was at a peak approximately 1 min after the start of irradiation, indicating that most of the ICG in the root canal was consumed. This study shows that aPDT/PACT can suppress E. faecalis in infected root canals with high efficiency.


Assuntos
Biofilmes/efeitos dos fármacos , Enterococcus faecalis/efeitos dos fármacos , Verde de Indocianina/administração & dosagem , Nanosferas , Fármacos Fotossensibilizantes/administração & dosagem , Animais , Enterococcus faecalis/fisiologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Verde de Indocianina/farmacologia , Lasers Semicondutores , Nanosferas/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Suínos
9.
ACS Appl Mater Interfaces ; 13(33): 38979-38989, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433249

RESUMO

Chronic infections caused by Pseudomonas aeruginosa pose severe threats to human health. Traditional antibiotic therapy has lost its total supremacy in this battle. Here, nanoplatforms activated by the clinical microenvironment are developed to treat P. aeruginosa infection on the basis of dynamic borate ester bonds. In this design, the nanoplatforms expose targeted groups for bacterial capture after activation by an acidic infection microenvironment, resulting in directional transport delivery of the payload to bacteria. Subsequently, the production of hyperpyrexia and reactive oxygen species enhances antibacterial efficacy without systemic toxicity. Such a formulation with a diameter less than 200 nm can eliminate biofilm up to 75%, downregulate the level of cytokines, and finally promote lung repair. Collectively, the biomimetic design with phototherapy killing capability has the potential to be an alternative strategy against chronic infections caused by P. aeruginosa.


Assuntos
Antibacterianos/química , Verde de Indocianina/química , Nanocápsulas/química , Fármacos Fotossensibilizantes/química , Polímeros/química , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/radioterapia , Células A549 , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Composição de Medicamentos , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Humanos , Verde de Indocianina/farmacologia , Raios Infravermelhos , Masculino , Metacrilatos/química , Camundongos Endogâmicos BALB C , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Pseudomonas aeruginosa/efeitos dos fármacos
10.
ACS Appl Mater Interfaces ; 13(33): 39112-39125, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34384220

RESUMO

Autophagy inhibition could hinder the underlying protective mechanisms in the course of tumor treatment. The advances in autophagy inhibition have driven focus on the functionalized nanoplatforms by combining the current treatment paradigms with complementary autophagy inhibition for enhanced efficacy. Furthermore, Ca2+ overload is also a promising adjuvant target for the tumor treatment by augmenting mitochondrial damage. In this view, complementary mitochondrial Ca2+ overload and autophagy inhibition were first demonstrated as a novel strategy suitable for homing in on the shortage of photodynamic therapy (PDT). We constructed biodegradable tumor-targeted inorganic/organic hybrid nanocomposites (DPGC/OI) synchronously encapsulating IR780 and Obatoclax by biomineralization of the nanofilm method, which consists of pH-triggered calcium phosphate (CP), long circulation phospholipid block copolymers 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-poly(ethylene glycol) (PEG)2000-glucose (DPG). In the presence of the hydrophilic PEG chain and glucose transporter 1 (Glut-1) ligands, DPGC would become an effectively tumor-oriented nanoplatform. Subsequently, IR780 as an outstanding photosensitizer could produce increased amounts of toxic reactive oxygen species (ROS) after laser irradiation. Calcium phosphate (CP) as the Ca2+ nanogenerator could generate Ca2+ at low pH to induce mitochondrial Ca2+ overload. The dysfunction of mitochondria could enhance increased amounts of ROS. Based on the premise that autophagy would degrade dysfunctional organelles to sustain metabolism and homeostasis, which might participate in resistance to PDT, Obatoclax as an autophagy inhibitor would hinder the protective mechanism from cancer cells with negligible toxicity. Such an enhanced PDT via mitochondrial Ca2+ overload and autophagy inhibition could be realized by DPGC/OI.


Assuntos
Autofagia/efeitos dos fármacos , Fosfatos de Cálcio/química , Glucose/química , Indóis/química , Nanocompostos/química , Fosfatidiletanolaminas/química , Fármacos Fotossensibilizantes/química , Polietilenoglicóis/química , Animais , Transporte Biológico , Melhoramento Biomédico , Feminino , Humanos , Indóis/metabolismo , Indóis/farmacologia , Camundongos Endogâmicos BALB C , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fosfolipídeos/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Pirróis/química , Pirróis/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Propriedades de Superfície , Distribuição Tecidual
11.
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
12.
Molecules ; 26(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34443298

RESUMO

Naphthodianthrones such as fagopyrin and hypericin found mainly in buckwheat (Fagopyrum spp.) and St. John's wort (SJW) (Hypericum perforatum L.) are natural photosensitizers inside the cell. The effect of photosensitizers was studied under dark conditions on growth, morphogenesis and induction of death in Saccharomyces cerevisiae. Fagopyrin and hypericin induced a biphasic and triphasic dose response in cellular growth, respectively, over a 10-fold concentration change. In fagopyrin-treated cells, disruptions in the normal cell cycle progression were evident by microscopy. DAPI staining revealed several cells that underwent premature mitosis without budding, a striking morphological abnormality. Flow Cytometric (FC) analysis using a concentration of 100 µM showed reduced cell viability by 41% in fagopyrin-treated cells and by 15% in hypericin-treated cells. FC revealed the development of a secondary population of G1 cells in photosensitizer-treated cultures characterized by small size and dense structures. Further, we show that fagopyrin and the closely related hypericin altered the shape and the associated fluorescence of biofilm-like structures. Colonies grown on solid medium containing photosensitizer had restricted growth, while cell-to-cell adherence within the colony was also affected. In conclusion, the photosensitizers under dark conditions affected culture growth, caused toxicity, and disrupted multicellular growth, albeit with different efficiencies.


Assuntos
Antracenos/farmacologia , Corantes/farmacologia , Perileno/análogos & derivados , Fármacos Fotossensibilizantes/farmacologia , Plâncton/crescimento & desenvolvimento , Quinonas/farmacologia , Saccharomycetales/crescimento & desenvolvimento , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fluorescência , Morfogênese/efeitos dos fármacos , Perileno/farmacologia , Plâncton/efeitos dos fármacos , Saccharomycetales/citologia , Saccharomycetales/efeitos dos fármacos
13.
Int J Mol Sci ; 22(16)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34445798

RESUMO

The bacterium Legionella pneumophila is still one of the probable causes of waterborne diseases, causing serious respiratory illnesses. In the aquatic systems, L. pneumophila exists inside free-living amoebae or can form biofilms. Currently developed disinfection methods are not sufficient for complete eradication of L. pneumophila biofilms in water systems of interest. Photodynamic inactivation (PDI) is a method that results in an antimicrobial effect by using a combination of light and a photosensitizer (PS). In this work, the effect of PDI in waters of natural origin and of different hardness, as a treatment against L. pneumophila biofilm, was investigated. Three cationic tripyridylporphyrins, which were previously described as efficient agents against L. pneumophila alone, were used as PSs. We studied how differences in water hardness affect the PSs' stability, the production of singlet oxygen, and the PDI activity on L. pneumophila adhesion and biofilm formation and in biofilm destruction. Amphiphilic porphyrin showed a stronger tendency for aggregation in hard and soft water, but its production of singlet oxygen was higher in comparison to tri- and tetracationic hydrophilic porphyrins that were stable in all water samples. All three studied porphyrins were shown to be effective as PDI agents against the adhesion of the L. pneumophila to polystyrene, against biofilm formation, and in the destruction of the formed biofilm, in their micromolar concentrations. However, a higher number of dissolved ions, i.e., water hardness, generally reduced somewhat the PDI activity of all the porphyrins at all tested biofilm growth stages.


Assuntos
Biofilmes/efeitos dos fármacos , Cátions/farmacologia , Dureza/efeitos dos fármacos , Legionella pneumophila/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Água/química , Amoeba/microbiologia , Oxigênio Singlete/farmacologia , Microbiologia da Água
14.
Anal Chem ; 93(35): 12059-12066, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34433261

RESUMO

Considering the multiple biological barriers before the entry of photosensitizers (PSs) into cytoplasm, it is of paramount importance to track PSs to elucidate their behaviors and distributions to guide the photodynamic therapy (PDT). Also, the developed PSs suffer from strong oxygen dependency. However, reports on such ideal theranostic platforms are rare. Herein, we developed a theranostic platform (CMTP-2) based on the coumarin-based D-π-A system, which, for the first time, can reveal the holistic intracellular delivery pathway and near-infrared (NIR)-activated mitophagy to guide synergistic type-I PDT and photothermal therapy. The dynamic endo-lysosomal escape of CMTP-2 was monitored, as well as its changeable distributions in endosomes, lysosomes, and mitochondria, demonstrating the preferential accumulation in mitochondria at the end. Upon NIR-I irradiation, CMTP-2 generated toxic radicals and heat, triggering the execution of mitophagy and apoptosis. In vivo experiments on mice indicated that CMTP-2 under 808 nm irradiation realized complete cancer ablation, showing great potential for advancements in synergistic phototherapy.


Assuntos
Mitofagia , Fotoquimioterapia , Animais , Linhagem Celular Tumoral , Lisossomos , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia , Terapia Fototérmica
15.
Photodiagnosis Photodyn Ther ; 35: 102459, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34320427

RESUMO

In this manuscript, we report, the photophysical study of triplet excited states and antimicrobial photoinactivation of positively charged tetra-cisplatin porphyrin derivatives against Gram + and Gram ‒ bacterial strains. Isomeric cisplatin-porphyrins were used and applied in aPDT assays in the bacilli Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa (Gram negative) and a cocci Staphylococcus aureus (Gram positive) strains. The results show that compound substituted at meta position (3-cis-PtTPyP) is the more efficient photosensitizer against bacteria culture. In this way, tetra-cationic porphyrins containing cisplatin derivatives might be promising aPDT agents with potential applications in clinical infections.


Assuntos
Anti-Infecciosos , Fotoquimioterapia , Porfirinas , Cisplatino , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia
16.
Photodiagnosis Photodyn Ther ; 35: 102464, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34320428

RESUMO

BACKGROUND: The aim of this study was to evaluate curcumin-mediated antimicrobial photodynamic therapy (aPDT) action combined or not with ethylenediaminetetraacetic acid (EDTA) and hydroxyethylidene bisphosphonate (HEBP) on Enterococcus faecalis biofilms. METHODS: Enterococcus faecalis biofilms were grown on dentin bovine discs in brain heart infusion (BHI) medium with 1% glucose, in aerobic conditions at 37°C for 7 days. Then, they were randomly distributed to one of experimental conditions, as follows: control, 75 J.cm-2 LED, 600 µmol.L-1 curcumin, 17% EDTA, 18% HEBP, 600 µmol.L-1 curcumin plus 75 J.cm-2 LED, 600 µmol.L-1 curcumin plus 17% EDTA, 600 µmol.L-1 curcumin plus 18% HEBP, 600 µmol.L-1 curcumin plus 17% EDTA and 75 J.cm-2 LED or 600 µmol.L-1 curcumin plus 18% HEBP and 75 J.cm-2 LED. The viability of microorganisms and the vitality of biofilms were determined by colony forming unit counts and confocal scanning laser microscopy (CSLM), respectively. Statistical analysis was conducted by Kruskal Wallis and Dunn's post-hoc tests (α = 0.05). RESULTS: The results showed that all combinations of aPDT with chelators significantly reduced the viability of microbial cells and the vitality of biofilms in comparison to control, even when considering deeper layers of biofilms. CONCLUSION: The combination of curcumin with EDTA and HEBP similarly improved the effect of aPDT on E. faecalis biofilms.


Assuntos
Anti-Infecciosos , Curcumina , Fotoquimioterapia , Animais , Anti-Infecciosos/uso terapêutico , Biofilmes , Bovinos , Quelantes/farmacologia , Curcumina/farmacologia , Enterococcus faecalis , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico
17.
Photodiagnosis Photodyn Ther ; 35: 102463, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34325078

RESUMO

The novel approach for imaging of antimicrobial photodynamic therapy processes presented in this work is based on transmission electron microscopy methods. With the use of liquid cell, illumination system, and lowered electron dose the successful light-induced in-situ observations on Staphylococcus aureus encapsulated with methylene blue were performed. Results showed that with specified imaging parameters it is possible to conduct reliable research on bacteria in electron microscope despite the unfavorable damaging effect of the highly energetic electron beam used for imaging. This approach differs from the common methods, as it provides direct observations of the processes occurring upon light illumination. The effects obtained with the proposed method are very promising and may serve to answer why different microorganisms respond to the therapy differently.


Assuntos
Anti-Infecciosos , Fotoquimioterapia , Azul de Metileno/farmacologia , Azul de Metileno/uso terapêutico , Microscopia Eletrônica de Transmissão , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico
18.
Photodiagnosis Photodyn Ther ; 35: 102458, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34325079

RESUMO

Water pollution and bacterial resistance are universal problems. Drugs and protocols have been employed to deal with involved microbes and pollutants but these customary chemicals have many limitations. It is essential to produce new methods and materials to deal with these deleterious microbes. In the present contribution, highly efficient and stable nanocomposite of platinum activated zinc oxide was synthesized by a new plant extract and surfactant assisted protocol. The cetylpyridinium chloride was applied as surfactant to obtain high dispersion of spherical ZnO. The platinum ions were reduced on the ZnO surface by the use of Rhazya stricta plant extract. The prepared nanomaterial was used for photoinactivation of multidrug resistant bacterium Escherichia coli (E. coli). The synthesized nanomaterial showed strong E. coli inhibition efficiency in the presence of light and the observed diameter of zone of inhibition was 21 ±0.4. The effect of light on the inhibition of E.coli was studied by measuring the activated oxygen radicals inside the bacterium cell. The surface morphology of E.coli before and after treatment with Pt/ZnO was studied by SEM. Such effect was not observed in dark. The toxicity of the synthesized nanomaterials was also studied through haemolytic activity and the result shows that the nanomaterial prepared by the said method has very low toxicity. The photocatalytic degradation of methylene blue (MB) was also investigated in the presence of the synthesized nanomaterials. Effect of different parameters such as concentration of Pt/ZnO, Irradiation time and dye concentrations were also studied. An incredible photocatalytic deprivation of MB (98 %) was observed for Pt/ZnO nanocomposite as compared to individual Pt (48%) and ZnO (71%) nanoparticles after 5 minutes of irradiations. Further research is required to investigate the applications of Pt/ZnO nanocomposite.


Assuntos
Nanocompostos , Fotoquimioterapia , Óxido de Zinco , Catálise , Escherichia coli , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Tensoativos
19.
Acta Biomater ; 131: 483-492, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34265471

RESUMO

Photodynamic therapy (PDT), where a photosensitizer (under light irradiation) converts molecular oxygen to singlet oxygen to elicit programmed cell death, is a promising cancer treatment modality with a high temporal and spatial resolution. However, only limited cancer treatment efficacy has been achieved in clinical PDT due to the hypoxic conditions of solid tumor microenvironment that limits the generation of singlet oxygen, and PDT process often leads to even more hypoxic microenvironment due to the consumption of oxygens during therapy. Herein, we designed novel supramolecular micelles to co-deliver photosensitizer and hypoxia-responsive prodrug to improve the overall therapeutic efficacy. The supramolecular micelles (CPC) were derived from a polyethylene glycol (PEG) system dually tagged with hydrophilic cucurbit[7]uril (CB[7]) and hydrophobic Chlorin e6 (Ce6), respectively on each end, for synergistic antitumor therapy via PDT of Ce6 and chemotherapy of a hypoxia-responsive prodrug, banoxantrone (AQ4N), loaded into the cavity of CB[7]. In addition, CPC was further modularly functionalized by folate (FA) via strong host-guest interaction between folate-amantadine (FA-ADA) and CB[7] to produce a novel nanoplatform, AQ4N@CPC-FA, for targeted delivery. AQ4N@CPC-FA exhibited enhanced cellular uptake, negligible cytotoxicity and good biocompatibility, and improved intracellular reactive oxygen species (ROS) generation efficiency. More importantly, in vivo evaluation of AQ4N@CPC-FA revealed a synergistic antitumor efficacy between PDT of Ce6 and hypoxia-activated chemotherapy of AQ4N (that can be converted to chemotherapeutic AQ4 for tumor chemotherapy in response to the strengthened hypoxic tumor microenvironment during PDT treatment). This study not only provides a new nanoplatform for synergistic photodynamic-chemotherapeutic treatment, but also offers important new insights to design and development of multifunctional supramolecular drug delivery system. STATEMENT OF SIGNIFICANCE: Photodynamic therapy (PDT) has exhibited a variety of advantages for cancer phototherapy as compared to traditional chemotherapy. However, the unsatisfactory therapeutic efficacy by PDT alone as a result of the enhanced tumor hypoxia during PDT has limited its clinical application. Herein, we designed multifunctional supramolecular micelles to co-deliver photosensitizer and hypoxia-responsive prodrug to improve the overall therapeutic efficacy. The supramolecular micelles are biocompatible and possess strong red absorption, controlled drug release profile, and ultimately enhanced therapeutic outcome via PDT-chemotherapy. This study not only provides a new nanoplatform for synergistic photodynamic-chemotherapeutic treatment of cancer, but also offers important new insights to design and development of multifunctional supramolecular drug delivery tool for multi-modality cancer therapy.


Assuntos
Antineoplásicos , Fotoquimioterapia , Linhagem Celular Tumoral , Humanos , Hipóxia , Micelas , Fármacos Fotossensibilizantes/farmacologia , Medicina de Precisão
20.
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
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