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1.
Toxicology ; 504: 153793, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574843

RESUMO

Photodynamic therapy (PDT) utilizes the potential of photosensitizing substances to absorb light energy and produce reactive oxygen species. Tetra-cationic porphyrins, which have organic or coordination compounds attached to their periphery, are heterocyclic derivatives with well-described antimicrobial and antitumoral properties. This is due to their ability to produce reactive oxygen species and their photobiological properties in solution. Consequently, these molecules are promising candidates as new and more effective photosensitizers with biomedical, environmental, and other biomedical applications. Prior to human exposure, it is essential to establish the toxicological profile of these molecules using in vivo models. In this study, we used Caenorhabditis elegans, a small free-living nematode, as a model for assessing toxic effects and predicting toxicity in preclinical research. We evaluated the toxic effects of porphyrins (neutral and tetra-cationic) on nematodes under dark/light conditions. Our findings demonstrate that tetra-methylated porphyrins (3TMeP and 4TMeP) at a concentration of 3.3 µg/mL (1.36 and 0.93 µM) exhibit high toxicity (as evidenced by reduced survival, development, and locomotion) under dark conditions. Moreover, photoactivated tetra-methylated porphyrins induce higher ROS levels compared to neutral (3TPyP and 4TPyP), tetra-palladated (3PdTPyP and 4PdTPyP), and tetra-platinated (3PtTPyP and 4PtTPyP) porphyrins, which may be responsible for the observed toxic effects.


Assuntos
Caenorhabditis elegans , Luz , Fármacos Fotossensibilizantes , Porfirinas , Animais , Caenorhabditis elegans/efeitos dos fármacos , Porfirinas/toxicidade , Porfirinas/química , Fármacos Fotossensibilizantes/toxicidade , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Fotoquimioterapia/métodos , Cátions/toxicidade , Relação Dose-Resposta a Droga
2.
Toxicology ; 495: 153613, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37558156

RESUMO

Although photosensitization remains a major toxicological endpoint for the safety assessment of cosmetic products and their raw materials, there is no validated in vitro method available for the evaluation of this adverse effect so far. Given that previous studies have proposed that the Interleukine-18 (IL-18) plays a key role in keratinocyte-driven pro-inflammatory responses specific of the skin sensitization process, we hypothesize that IL-18 might be used as a specific biomarker for in vitro photosensitization assessment. The aim of the present study was the set-up of a new in vitro assay using IL-18 as a biomarker for the identification of photosensitizers in a reconstructed human epidermis (RHE) model. EpiCS™ RHE were incubated with a set of 16 known sensitising / phototoxic / photosensitizing substances and exposed to ultra-violet (UV) irradiation. Then, the cell viability was analysed by MTT assay, while the IL-18 secretion was quantified by ELISA. Preliminary assays have shown that 1 h of incubation followed by a recovery period of 23 h induced the highest IL-18 production in response to UV exposure. This protocol was used to test 16 substances and a ratio of IL-18 production (UV+/UV- ratio) was then generated. Our data shows that the cut-off of 1.5 (UV+/UV- ratio) is the most predictive model among the tested conditions, being capable of identifying true positive photosensitizers (8 of 9) with a good prediction in comparison with in vivo data. In a nutshell, our data suggests that the PhotoSENSIL-18 is a promising in vitro method for identification of photosensitizing substances. Although further studies are necessary to optimize the model, we foresee that the PhotoSENSIL-18 assay can be used in the context of an Integrative Approach to Testing and Assessment (IATA) of chemicals.


Assuntos
Dermatite Fototóxica , Interleucina-18 , Humanos , Animais , Interleucina-18/farmacologia , Fármacos Fotossensibilizantes/toxicidade , Epiderme , Queratinócitos , Pele , Alternativas aos Testes com Animais
3.
Environ Pollut ; 334: 121738, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37121304

RESUMO

The spread of antibiotic resistant bacteria from wastewater to the environment will pose serious threats to human health. It is a potential solution to prepare photosensitizers with broad-spectrum antibacterial activity for use in the photo-oxidation process to supplement the wastewater treatment system. Here, an aggregation-induced emission photosensitizer with D-π-A structure (TBTPy) has been reasonably designed and successfully developed. TBTPy can generate singlet oxygen with extraordinarily high efficiency under white-light irradiation owing to the small singlet-triplet energy gap. TBTPy has a rapid and efficient photo-oxidative killing effect on bacteria and fungi (such as MRSA, S. aureus, E. coli and C. albicans). TBTPy kills bacteria by binding to bacterial surface and releasing singlet oxygen to destroy cell membrane, leading to leakage of bacterial genetic material. This successful case can provide practical guidance for the subsequent development of AIE photosensitizers.


Assuntos
Fármacos Fotossensibilizantes , Staphylococcus aureus , Humanos , Fármacos Fotossensibilizantes/toxicidade , Fármacos Fotossensibilizantes/química , Escherichia coli , Águas Residuárias , Antibacterianos/toxicidade , Antibacterianos/química , Oxigênio Singlete , Bactérias
4.
Chemosphere ; 325: 138362, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36905996

RESUMO

The removal of antibiotics in wastewater has attracted increasing attention. Herein, a superior photosensitized photocatalytic system was developed with acetophenone (ACP) as the guest photosensitizer, bismuth vanadate (BiVO4) as the host catalyst and poly dimethyl diallyl ammonium chloride (PDDA) as the bridging complex, and used for the removal of sulfamerazine (SMR), sulfadiazine (SDZ) and sulfamethazine (SMZ) in water under simulated visible light (λ > 420 nm). The obtained ACP-PDDA-BiVO4 nanoplates attained a removal efficiency of 88.9%-98.2% for SMR, SDZ and SMZ after 60 min reaction and achieved kinetic rate constant approximately 10, 4.7 and 13 times of BiVO4, PDDA-BiVO4 and ACP-BiVO4, respectively, for SMZ degradation. In the guest-host photocatalytic system, ACP photosensitizer was found to have a great superiority in enhancing the light absorption, promoting the surface charge separation-transfer and efficient generation of holes (h+) and superoxide radical (·O2-), greatly contributing to the photoactivity. The SMZ degradation pathways were proposed based on the identified degradation intermediates, involving three main pathways of rearrangement, desulfonation and oxidation. The toxicity of intermediates was evaluated and the results demonstrated that the overall toxicity was reduced compared with parent SMZ. This catalyst maintained 92% photocatalytic oxidation performance after five cyclic experiments and displayed a co-photodegradation ability to others antibiotics (e.g., roxithromycin, ciprofloxacin et al.) in effluent water. Therefore, this work provides a facile photosensitized strategy for developing guest-host photocatalysts, which enabling the simultaneous antibiotics removal and effectively reduce the ecological risks in wastewater.


Assuntos
Antibacterianos , Fármacos Fotossensibilizantes , Antibacterianos/toxicidade , Fotólise , Fármacos Fotossensibilizantes/toxicidade , Águas Residuárias , Luz , Bismuto , Vanadatos/toxicidade , Sulfametazina , Sulfadiazina , Sulfamerazina , Água , Catálise
5.
Saudi J Gastroenterol ; 29(1): 53-58, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36571385

RESUMO

Background: Methylene blue (MB) is used endoscopically to demarcate tumors and as a photosensitizer in photodynamic therapy (PDT). However, there are few in vivo studies about its toxicity in healthy stomach tissue. We performed sequential in vitro and in vivo analyses of MB-induced phototoxicity. Methods: We performed in vitro experiments using the AGS human gastric cancer cell line treated with light-emitting diode (LED) irradiation (3.6 J/cm2) and MB. Cytotoxicity was evaluated using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. In vivo toxicity was evaluated in the stomach of beagles using the same dose of fiber-optic LED via gastroscopy, after spraying 0.1% and 0.5% MB solutions. Stomach tissue was also evaluated using the TUNEL assay. Results: In vitro, increased concentrations of MB led to higher TUNEL scores. However, cell viability was significantly lower after MB plus LED irradiation than after treatment with MB alone (P < 0.001). In vivo, the TUNEL score was highest immediately after treatment with 0.1% or 0.5% MB plus light irradiation, and the score was significantly higher in the LED illumination plus MB group than in the control group (P < 0.05). The elevated TUNEL score was maintained for 3 days in the MB plus light irradiation group but returned to normal levels on day 10. Conclusions: : Endoscopic light application with MB 0.5% concentration to the stomach may be regarded as a safe procedure despite some DNA injuries in the early period.


Assuntos
Azul de Metileno , Fotoquimioterapia , Cães , Animais , Humanos , Azul de Metileno/farmacologia , Azul de Metileno/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/toxicidade , Fármacos Fotossensibilizantes/uso terapêutico , Linhagem Celular , Mucosa Gástrica
6.
Environ Pollut ; 311: 120015, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36007787

RESUMO

The control of multidrug-resistant bacteria (MDRB) is a great challenge in the 21st century. Photodynamic treatment (PDT) is one of the promising approaches to control MDRB. In the process, powerful oxidants such as reactive oxygen species (ROS) are produced, which cause cytotoxic damage and cell death of bacteria. This study examined a new and environment-friendly strategy for the photodynamic inactivation of two MDRB (Escherichia coli and Staphylococcus aureus) and total coliform (TC) in wastewater effluent using two phytochemicals, pyrogallol (PGL) and terpinolene (TPN), along with white and blue light-emitting diode (LED) light. Fourier-transform infrared spectroscopy (FTIR) of the phytochemicals confirmed the presence of different phenolic and aromatic compounds, which can enhance the generation of ROS alongside inactivating the bacterial cells. In the PDT process, white LED light was more active in controlling MDRB than blue LED light. After 80 min irradiation with white LED light (17 mW/cm2), the MDRB bacteria were eradicated completely at a minimum inhibitory concentration (MIC) dose (0.156 mg/mL for E. coli and 0.078 mg/mL for S. aureus) of PGL. In addition, light intensity was an important parameter in photodynamic disinfection. The TC in the secondary effluent was inactivated completely by both phytochemicals after 60 min of exposure to white LED light with an intensity of 80 mW/cm2. The photosensitizing activity of phytochemicals was analyzed by a bactericidal and imidazole-RNO assay. These assays showed that PGL contributed to the generation of •OH radicals, whereas TPN produced 1O2 in the PDT process. Transmission electron microscopy (TEM) confirmed bacterial cell disruption after treatment. Overall, PDT using the phytochemicals as PS is a sustainable approach to control the MDRB and TC in wastewater successfully.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Escherichia coli/metabolismo , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/toxicidade , Compostos Fitoquímicos , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus , Águas Residuárias
7.
J Nanobiotechnology ; 19(1): 454, 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34963479

RESUMO

Gold nanorods (GNRs) have a broad application prospect in biomedical fields because of their unique properties and controllable surface modification. The element aurum (Au) with high atomic number (high-Z) render GNRs ideal radiosensitive materials for radiation therapy and computed tomography (CT) imaging. Besides, GNRs have the capability of efficiently converting light energy to heat in the near-infrared (NIR) region for photothermal therapy. Although there are more and more researches on GNRs for radiation therapy, how to improve their biocompatibility and how to efficiently utilize them for radiation therapy should be further studied. This review will focuse on the research progress regarding the preparation and toxicity reduction of GNRs, as well as GNRs-mediated radiation therapy.


Assuntos
Ouro/química , Nanotubos/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Radioterapia , Animais , Ouro/uso terapêutico , Ouro/toxicidade , Humanos , Hipertermia Induzida , Nanotubos/toxicidade , Fármacos Fotossensibilizantes/toxicidade , Terapia Fototérmica
8.
ACS Appl Mater Interfaces ; 13(41): 48433-48448, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34613687

RESUMO

The excessive colonization of Propionibacterium acnes (P. acnes) is responsible for the genesis of acne vulgaris, a common inflammatory disease of skin. However, the conventional anti-acne therapies are always limited by various side effects, drug resistance, and poor skin permeability. Microneedles (MNs) are emerging topical drug delivery systems capable of noninvasively breaking through the skin stratum corneum barrier to efficiently enhance the transdermal drug penetration. Herein, MNs loaded with intelligent pH-sensitive nanoplatforms were constructed for amplified chemo-photodynamic therapy against acne vulgaris, jointly exerting antimicrobial and anti-inflammatory effects. The photosensitizer indocyanine green (ICG) was loaded into the zeolitic imidazolate framework-8 (ZIF-8) to improve its photostability, which would be triggered by 808 nm laser irradiation to generate cytotoxic reactive oxygen species (ROS) to result in oxidative damage and disturbed metabolic activities of P. acnes. In addition to the efficient drug delivery, the ZIF-8 carrier could selectively degrade in response to the acidic microenvironment of acne lesions, and the released Zn2+ also exhibited a potent antimicrobial activity. The fabricated ZIF-8-ICG@MNs presented an outstanding synergistic anti-acne efficiency both in vitro and in vivo. This bioresponsive microneedle patch is expected to be readily adapted as a generalized, modular strategy for noninvasive therapeutics delivery against superficial skin diseases.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Imidazóis/uso terapêutico , Verde de Indocianina/uso terapêutico , Estruturas Metalorgânicas/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Acne Vulgar/patologia , Animais , Antibacterianos/química , Antibacterianos/efeitos da radiação , Antibacterianos/toxicidade , Anti-Inflamatórios/química , Anti-Inflamatórios/efeitos da radiação , Anti-Inflamatórios/toxicidade , Células HEK293 , Humanos , Imidazóis/química , Imidazóis/efeitos da radiação , Imidazóis/toxicidade , Verde de Indocianina/química , Verde de Indocianina/efeitos da radiação , Verde de Indocianina/toxicidade , Raios Infravermelhos , Masculino , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/efeitos da radiação , Estruturas Metalorgânicas/toxicidade , Camundongos Endogâmicos BALB C , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidade , Propionibacterium acnes/efeitos dos fármacos , Ratos , Pele/efeitos dos fármacos , Pele/patologia , Suínos , Zinco/química , Zinco/efeitos da radiação , Zinco/uso terapêutico , Zinco/toxicidade
9.
ACS Appl Mater Interfaces ; 13(38): 45201-45213, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34525803

RESUMO

Overproduction of reactive oxygen species (ROS) within tumors can cause oxidative stress on tumor cells to induce death, which has motivated us to develop ROS-mediated tumor therapies, such as typical photodynamic therapy (PDT) and Fenton reaction-mediated chemodynamic therapy (CDT). However, these therapeutic modalities suffer from compromised treatment efficacy owing to their limited generation of highly reactive ROS in a tumor microenvironment (TME). In this work, a nanoscale iron-based metal-organic framework, MIL-101(Fe), is synthesized as a Fenton nanocatalyst to perform the catalytic conversion of hydroxyl radicals (·OH) from hydrogen peroxide (H2O2) under the acidic environment and as a biocompatible and biodegradable nanocarrier to deliver a 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) photosensitizer for light-activated singlet oxygen (1O2) generation. By coupling such chemodynamic/photodynamic effects, the photosensitizer-integrated nanoagents (MIL-101(Fe)@TCPP) could enable more ROS production within tumors to induce amplified oxidative damage for tumor-specific synergistic therapy. In vitro results show that MIL-101(Fe)@TCPP nanoagents achieve the acid-responsive CDT and effective PDT, and synergistic CDT/PDT provides an enhanced therapeutic effect. Ultimately, based on such synergistic therapy, MIL-101(Fe)@TCPP nanoagents cause a significant tumor growth inhibition in vivo without severe side effects, showing great potential for anti-tumor application.


Assuntos
Antineoplásicos/uso terapêutico , Estruturas Metalorgânicas/uso terapêutico , Nanoestruturas/uso terapêutico , Neoplasias/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fármacos Fotossensibilizantes/uso terapêutico , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Catálise , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/química , Radical Hidroxila/metabolismo , Ferro/química , Luz , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Estruturas Metalorgânicas/toxicidade , Nanoestruturas/química , Nanoestruturas/toxicidade , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidade , Porfirinas/farmacologia , Porfirinas/efeitos da radiação , Porfirinas/uso terapêutico , Porfirinas/toxicidade , Oxigênio Singlete/metabolismo
10.
Chem Commun (Camb) ; 57(71): 8993-8996, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34486606

RESUMO

The oxidative phosphorylation inhibitor atovaquone (ATO) and the photosensitizer new indocyanine green (IR820) were self-assembled into carrier-free nanodrugs (IR820/ATO NPs) to achieve superior photothermal therapy (PTT), offering an attractive mitochondrial metabolism-regulatable approach for breast cancer treatment, where adenosine triphosphate (ATP) was downregulated along with downregulating the expression of heat shock proteins (HSPs) to amplify the sensitivity of PTT.


Assuntos
Antineoplásicos/farmacologia , Atovaquona/farmacologia , Neoplasias da Mama/tratamento farmacológico , Verde de Indocianina/análogos & derivados , Nanopartículas/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Atovaquona/química , Atovaquona/toxicidade , Linhagem Celular Tumoral , Feminino , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Verde de Indocianina/toxicidade , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Nanopartículas/química , Nanopartículas/toxicidade , Fosforilação Oxidativa/efeitos dos fármacos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/toxicidade , Terapia Fototérmica
11.
ACS Appl Mater Interfaces ; 13(36): 42396-42410, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34472332

RESUMO

Chronic wound healing, impeded by bacterial infections and drug resistance, poses a threat to global human health. Antibacterial phototherapy is an effective way to fight microbial infection without causing drug resistance. Covalent organic frameworks (COFs) are a class of highly crystalline functional porous carbon-based materials composed of light atoms (e.g., carbon, nitrogen, oxygen, and borane), showing potential applications in the biomedical field. Herein, we constructed porphyrin-based COF nanosheets (TP-Por CON) for synergizing photodynamic and photothermal therapy under red light irradiation (e.g., 635 nm). Moreover, a nitric oxide (NO) donor molecule, BNN6, was encapsulated into the pore volume of the crystalline porous framework structure to moderately release NO triggered by red light irradiation for realizing gaseous therapy. Therefore, we successfully synthesized a novel TP-Por CON@BNN6-integrated heterojunction for thoroughly killing Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus in vitro. Our research identified that TP-Por CON@BNN6 has favorable biocompatibility and biodegradability, low phototoxicity, anti-inflammatory properties, and excellent mice wound healing ability in vivo. This study indicates that the TP-Por CON@BNN6-integrated heterojunction with multifunctional properties provides a potential strategy for COF-based gaseous therapy and microorganism-infected chronic wound healing.


Assuntos
Anti-Inflamatórios/uso terapêutico , Estruturas Metalorgânicas/uso terapêutico , Doadores de Óxido Nítrico/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Anti-Inflamatórios/efeitos da radiação , Anti-Inflamatórios/toxicidade , Linhagem Celular , Escherichia coli/efeitos dos fármacos , Luz , Estruturas Metalorgânicas/efeitos da radiação , Estruturas Metalorgânicas/toxicidade , Camundongos Endogâmicos BALB C , Doadores de Óxido Nítrico/efeitos da radiação , Doadores de Óxido Nítrico/toxicidade , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidade , Porfirinas/efeitos da radiação , Porfirinas/uso terapêutico , Porfirinas/toxicidade , Staphylococcus aureus/efeitos dos fármacos
12.
ACS Appl Mater Interfaces ; 13(31): 37665-37679, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34342216

RESUMO

Nanoscale hydroxyapatite (nHA) is considered as a promising drug carrier or therapeutic agent against malignant tumors. But the strong agglomeration tendency and lack of active groups seriously hamper their usage in vivo. To address these issues, we fabricated an organic-inorganic hybrid nanosystem composed of poly(acrylic acid) (PAA), nHA, and indocyanine green (ICG), and further modified with glucose to give a targeting nanosystem (GA@HAP/ICG-NPs). These hybrid nanoparticles (∼90 nm) showed excellent storage and physiological stability assisted by PAA and had a sustained drug release in an acidic tumor environment. In vitro cell experiments confirmed that glucose-attached particles significantly promoted cellular uptake and increased intracellular ICG and Ca2+ concentrations by glucose transporter 1 (GLUT1)-mediated endocytosis. Subsequently, the excessive Ca2+ induced cell or organelle damage and ICG triggered photothermal and photodynamic effects (PTT/PDT) under laser irradiation, resulting in enhanced cell toxicity and apoptosis. In vivo tests revealed that the hybrid nanosystem possessed good hemocompatibility and biosafety, facilitating in vivo circulation and usage. NIR imaging further showed that tumor tissues had more drug accumulation, resulting in the highest tumor growth inhibition (87.89%). Overall, the glucose-targeted hybrid nanosystem was an effective platform for collaborative therapy and expected to be further used in clinical trials.


Assuntos
Antineoplásicos/uso terapêutico , Durapatita/uso terapêutico , Verde de Indocianina/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Resinas Acrílicas/química , Resinas Acrílicas/toxicidade , Animais , Antineoplásicos/química , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Portadores de Fármacos/toxicidade , Durapatita/química , Durapatita/toxicidade , Glucose/química , Glucose/toxicidade , Células Hep G2 , Humanos , Verde de Indocianina/química , Verde de Indocianina/efeitos da radiação , Verde de Indocianina/toxicidade , Raios Infravermelhos , Masculino , Camundongos Endogâmicos ICR , Nanopartículas/química , Nanopartículas/efeitos da radiação , Nanopartículas/toxicidade , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidade , Terapia Fototérmica
13.
Carbohydr Polym ; 269: 118242, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34294284

RESUMO

To promote bactericidal activity, improve photostability and safety, novel antibacterial nanoparticle system based on photodynamic action (PDA) was prepared here through conjugation of photosensitizer hematoporphyrin (HP) onto carboxymethyl chitosan (CMCS) via amide linkage and followed by ultrasonic treatment. The system was stable in PBS (pH 7.4) and could effectively inhibit the photodegradation of conjugated HP because of aggregation-caused quenching effect. ROS produced by the conjugated HP under light exposure could change the structure of nanoparticles by oxidizing the CMCS skeleton and thereby significantly promote the photodynamic activity of HP and its photodynamic activity after 6 h was higher than that of HP·2HCl under the same conditions. Antibacterial experiments showed that CMCS-HP nanoparticles had excellent photodynamic antibacterial activity, and the bacterial inhibition rates after 60 min of light exposure were greater than 97%. Safety evaluation exhibited that the nanoparticles were safe to mammalian cells, showing great potential for antibacterial therapy.


Assuntos
Antibacterianos/farmacologia , Quitosana/análogos & derivados , Hematoporfirinas/farmacologia , Nanopartículas/química , Fármacos Fotossensibilizantes/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/efeitos da radiação , Antibacterianos/toxicidade , Quitosana/síntese química , Quitosana/farmacologia , Quitosana/efeitos da radiação , Quitosana/toxicidade , Escherichia coli/efeitos dos fármacos , Hematoporfirinas/síntese química , Hematoporfirinas/efeitos da radiação , Hematoporfirinas/toxicidade , Luz , Camundongos , Testes de Sensibilidade Microbiana , Células NIH 3T3 , Nanopartículas/efeitos da radiação , Nanopartículas/toxicidade , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus , Tensoativos/síntese química , Tensoativos/farmacologia , Tensoativos/efeitos da radiação , Tensoativos/toxicidade
14.
ACS Appl Mater Interfaces ; 13(30): 35568-35578, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34286585

RESUMO

Mitochondria-targeted synergistic therapy, including photothermal (PTT) and photodynamic therapy (PDT), has aroused wide attention due to the high sensitivity to reactive oxygen species (ROS) and heat shock of mitochondria. However, most of the developed nanosystems for the combinatorial functions require the integration of different components, such as photosensitizers and mitochondria-targeted molecules. Consequently, it indispensably requires sophisticated design and complex synthetic procedures. In this work, a well-designed Bi2S3-based nanoneedle, that localizes to mitochondria and produces extra ROS with inherent photothermal effect, was reported by doping of Fe (denoted as FeBS). The engineered intrinsic characteristics certify the capacity of such "one-for-all" nanosystems without additional molecules. The lipophilicity and surface positive charge are demonstrated as crucial factors for specifical mitochondria targeting. Significantly, Fe doping overcomes the disadvantage of the narrow band gap of Bi2S3 to prevent the fast recombination of electron-hole, hence resulting in the generation of ROS for PDT. The "one-for-all" nanoparticles integrate with mitochondria-targeting and synergistic effect of PDT and PTT, thus exhibit enhanced therapeutic effect and inhibit the growth of tumors observably. This strategy may open a new direction in designing the mitochondria-targeted materials and broadening the properties of inorganic semiconductor materials for satisfactory therapeutic outcomes.


Assuntos
Antineoplásicos/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Bismuto/química , Feminino , Células HeLa , Humanos , Ferro/química , Camundongos Endogâmicos BALB C , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/toxicidade , Terapia Fototérmica , Espécies Reativas de Oxigênio/metabolismo , Sulfetos/química
15.
ACS Appl Mater Interfaces ; 13(30): 35328-35341, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34291912

RESUMO

The multifunctional combined nanoplatform has a wide application prospect in the synergistic treatment of cancer. Nevertheless, the traditional treatment of phototherapy is limited by the catalytic nanomaterial itself, so the effect is not satisfactory. Here, the arris of the anisotropic truncated octahedral Au (TOh Au) was coated with noble metal Pt to form a spatial separation structure, which enhanced the local surface plasmonic resonance and thus boosted the photocatalytic effect. In this system, the highly efficient photocatalysis provides a strong guarantee for oncotherapy. On the one hand, the structure of arris deposition adequately improves the efficiency of photothermal conversion, which substantially improves the effectiveness of photothermal therapy. On the other hand, in situ oxygen production of Pt ameliorates tumor hypoxia, and through the O2 self-production and sales mode, the growth and development of tumor were inhibited. Meanwhile, under the enhanced photocatalysis, more O2 were produced, which greatly evolved the treatment effect of photodynamic therapy. In the end, the addition of hyaluronic acid can specifically target osteosarcoma cells while improving the retention time and biocompatibility of the material in the body. Thus, the nanocomposite shows superexcellent synergistic enhancement of photothermal conversion efficiency and photodynamic capability in vitro and in vivo, which provides a potential possibility for osteosarcoma cure.


Assuntos
Antineoplásicos/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Osteossarcoma/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Anisotropia , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Antineoplásicos/toxicidade , Catálise/efeitos da radiação , Clorofilídeos , Ouro/química , Ouro/toxicidade , Ácido Hialurônico/química , Ácido Hialurônico/toxicidade , Raios Infravermelhos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/efeitos da radiação , Nanopartículas Metálicas/toxicidade , Camundongos Nus , Osteossarcoma/metabolismo , Oxigênio/metabolismo , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidade , Terapia Fototérmica , Platina/química , Platina/toxicidade , Polietilenoglicóis/química , Polietilenoglicóis/toxicidade , Porfirinas/química , Porfirinas/efeitos da radiação , Porfirinas/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Ressonância de Plasmônio de Superfície
16.
Chemistry ; 27(59): 14672-14680, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34324228

RESUMO

In this contribution we report on the synthesis, characterization and application of water-soluble zinc(II) phthalocyanines, which are decorated with four or eight umbelliferone moieties for photodynamic therapy (PDT). These compounds are linked peripherally to zinc(II) phthalocyanine by a triethylene glycol linker attached to pyridines, leading to cationic pyridinium units, able to increase the water solubility of the system. Beside their photophysical properties they were analyzed concerning their cellular distribution in human hepatocyte carcinoma (HepG2) cells as well as their phototoxicity towards HepG2 cells, Gram-positive (S. aureus strain 3150/12 and B. subtilis strain DB104) and Gram-negative bacteria (E. coli strain UTI89 and E. coli strain Nissle 1917). At low light doses and concentrations, they exhibit superb antimicrobial activity against Gram-positive bacteria as well as anti-tumor activity against HepG2. They are even capable to inactivate Gram-negative bacteria, whereas the dark toxicity remains low. These unique water-soluble compounds can be regarded as all-in-one type photosensitizers with broad applications ranges in the future.


Assuntos
Anti-Infecciosos , Compostos Organometálicos , Fotoquimioterapia , Escherichia coli , Humanos , Isoindóis , Fármacos Fotossensibilizantes/toxicidade , Staphylococcus aureus , Umbeliferonas , Água , Zinco , Compostos de Zinco
17.
Toxicology ; 460: 152872, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34303732

RESUMO

The increasing number of tattooed persons urges the development of reliable test systems to assess tattoo associated risks. The alarming prevalence of 60 % phototoxic reactions in tattoos ask for a more comprehensive investigation of phototoxic reactions in tattooed skin. Here, we aimed to compare the cellular responses of human skin cells to ultraviolet (UV)A and UVB irradiation in doses of short to intermitted sun exposure (3-48 J/cm² and 0.05-5 J/cm², respectively) in the presence of tattoo pigments. Therefore, we used fibroblast monolayer culture (2D), our recently developed three dimensional full-thickness skin model with dermal-located tattoo pigments (TatSFT) and its dermal equivalents (TatSDE) that lack keratinocytes. We tested the most frequently used tattoo pigments carbon black, titanium dioxide (TiO2) anatase and rutile as well as Pigment Orange (P.O.)13 in ranges from 0.067 to 2.7 ng/cell in 2D. For TatSDE and TatSFT, concentrations were 1.3 ng/cell for TiO2, 0.67 ng/cell for P.O.13 and 0.067 ng/cell for carbon black. We assessed cell viability and cytokine release in all systems, and cyclobutane pyrimidine dimer (CPD) formation in TatSFT. Phototoxicity of tattoo pigments was exclusively observed in 2D, where especially TiO2 anatase induced phototoxic effects in all concentrations (0.067-2.7 ng/cell). In contrast, fibroblasts were protected from UV irradiation in TatSDE by TiO2 and carbon black. Neither toxic nor protective effects were recorded in TatSFT. P.O.13 showed altered cytokine secretion in 2D (0.067-1.3 ng/cell) and TatSDE, despite the absence of significant effects on viability in all systems. All pigments reduced the number of CPDs in TatSFT compared to the pigment-free controls. In conclusion, our study shows that within a 3D arrangement, intradermal tattoo pigments may act photoprotective despite intrinsic phototoxic properties in 2D. Thus, dermal 3D equivalents should be considered to evaluate acute tattoo pigment toxicology.


Assuntos
Corantes/toxicidade , Dermatite Fototóxica , Pele/efeitos dos fármacos , Tatuagem/efeitos adversos , Testes de Toxicidade/métodos , Raios Ultravioleta/efeitos adversos , Células Cultivadas , Corantes/farmacologia , Dermatite Fototóxica/patologia , Relação Dose-Resposta a Droga , Prepúcio do Pênis/citologia , Prepúcio do Pênis/efeitos dos fármacos , Prepúcio do Pênis/patologia , Humanos , Recém-Nascido , Masculino , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/toxicidade , Pele/patologia , Pele/efeitos da radiação , Fuligem/farmacologia , Fuligem/toxicidade , Tatuagem/métodos , Titânio/farmacologia , Titânio/toxicidade
18.
Int J Biol Macromol ; 187: 296-308, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34310998

RESUMO

Image-guided chemo-photothermal therapy based on near-infrared (NIR) theranostic agents has found promising applications in treating tumors. In this multimodal treatment, it is of critical importance to image real-time distribution of photothermal agents in vivo and to monitor therapeutic outcomes for implementing personalized treatment. In this study, an optimally synthesized dextran-polylactide (DEX-PLA) copolymer was assembled with doxorubicin (DOX) and DiR, a kind of NIR dye, to construct desirable micelles ((DiR + DOX)/DEX-PLA) for performing image-guided chemo-photothermal therapy. These (DiR + DOX)/DEX-PLA micelles had good physical and photothermal stability in aqueous media and showed high photothermal efficiency in vivo. Based on the H22-tumor-bearing mouse model, (DiR + DOX)/DEX-PLA micelles were found to accumulate inside tumors sustainably and to emit strong fluorescence signals for more than three days. The (DiR + DOX)@DEX-PLA micelles together with NIR laser irradiation were able to highly inhibit tumor growth or even eradicate tumors with one injection and two dose-designated 5-minute laser irradiations at the tumor site during 14 days of treatment. Furthermore, they showed almost no impairment to the body of the treated mice. These (DiR + DOX)@DEX-PLA micelles have confirmative translational potential in clinical tumor therapy on account of their persistent image-guided capacity, high antitumor efficacy and good in vivo safety.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Carbocianinas/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Dextranos/química , Doxorrubicina/administração & dosagem , Portadores de Fármacos , Corantes Fluorescentes/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Fármacos Fotossensibilizantes/administração & dosagem , Terapia Fototérmica , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/toxicidade , Carbocianinas/química , Carbocianinas/toxicidade , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Dextranos/toxicidade , Doxorrubicina/química , Doxorrubicina/toxicidade , Composição de Medicamentos , Corantes Fluorescentes/química , Corantes Fluorescentes/toxicidade , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos Endogâmicos BALB C , Micelas , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/toxicidade , Espectroscopia de Luz Próxima ao Infravermelho , Nanomedicina Teranóstica , Fatores de Tempo , Carga Tumoral/efeitos dos fármacos
19.
ACS Appl Mater Interfaces ; 13(26): 31193-31205, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34164984

RESUMO

Owing to the rise in prevalence of multidrug-resistant pathogens attributed to the overuse of antibiotics, infectious diseases caused by the transmission of microbes from contaminated surfaces to new hosts are an ever-increasing threat to public health. Thus, novel materials that can stem this crisis, while also functioning via multiple antimicrobial mechanisms so that pathogens are unable to develop resistance to them, are in urgent need. Toward this goal, in this work, we developed in situ grown bacterial cellulose/MoS2-chitosan nanocomposite materials (termed BC/MoS2-CS) that utilize synergistic membrane disruption and photodynamic and photothermal antibacterial activities to achieve more efficient bactericidal activity. The BC/MoS2-CS nanocomposite exhibited excellent antibacterial efficacy, achieving 99.998% (4.7 log units) and 99.988% (3.9 log units) photoinactivation of Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus, respectively, under visible-light illumination (xenon lamp, 500 W, λ ≥ 420 nm, and 30 min). Mechanistic studies revealed that the use of cationic chitosan likely facilitated bacterial membrane disruption and/or permeability, with hyperthermia (photothermal) and reactive oxygen species (photodynamic) leading to synergistic pathogen inactivation upon visible-light illumination. No mammalian cell cytotoxicity was observed for the BC/MoS2-CS membrane, suggesting that such composite nanomaterials are attractive as functional materials for infection control applications.


Assuntos
Antibacterianos/farmacologia , Dissulfetos/farmacologia , Molibdênio/farmacologia , Nanocompostos/química , Fármacos Fotossensibilizantes/farmacologia , Animais , Antibacterianos/química , Antibacterianos/efeitos da radiação , Antibacterianos/toxicidade , Linhagem Celular , Celulose/química , Celulose/toxicidade , Quitosana/química , Quitosana/toxicidade , Dissulfetos/química , Dissulfetos/efeitos da radiação , Dissulfetos/toxicidade , Escherichia coli/efeitos dos fármacos , Calefação , Luz , Membranas Artificiais , Camundongos , Testes de Sensibilidade Microbiana , Molibdênio/química , Molibdênio/efeitos da radiação , Molibdênio/toxicidade , Nanocompostos/efeitos da radiação , Nanocompostos/toxicidade , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos
20.
Carbohydr Polym ; 267: 118215, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34119169

RESUMO

This paper aims at providing a new strategy for developing konjac glucomannan-based antibacterial films with excellent performances. Here, novel nanocomposite films based on photodynamic and photothermal synergism strategy were developed by incorporating graphite carbon nitride nanosheets/MoS2 nanodots (CNMo) into konjac glucomannan (KGM) matrix. Scanning electron microscope, transmission electron microscope, high resolution transmission, high angle annular dark field and element mapping confirmed the successful fabrication of CNMo. The steady and dynamic rheological behavior as well as the good stability of film-forming solution showed that the intermolecular hydrogen bonding was formed. The influences of CNMo content on the structural, mechanical and thermal properties as well as hydrophobicity of KGM films were investigated. This film has a broad-spectrum antibacterial activity. It could prolong the shelf life of cherry tomatoes. Moreover, hemolysis and cells experiment confirm that this film is safe. This strategy is expected to broaden the application of antibacterial packaging.


Assuntos
Antibacterianos/farmacologia , Embalagem de Alimentos , Mananas/farmacologia , Nanocompostos/química , Animais , Antibacterianos/química , Antibacterianos/toxicidade , Dissulfetos/química , Dissulfetos/farmacologia , Dissulfetos/toxicidade , Escherichia coli/efeitos dos fármacos , Conservação de Alimentos/instrumentação , Grafite/química , Grafite/farmacologia , Grafite/toxicidade , Interações Hidrofóbicas e Hidrofílicas , Solanum lycopersicum , Mananas/química , Mananas/toxicidade , Camundongos , Testes de Sensibilidade Microbiana , Molibdênio/química , Molibdênio/farmacologia , Molibdênio/toxicidade , Células NIH 3T3 , Nanocompostos/toxicidade , Compostos de Nitrogênio/química , Compostos de Nitrogênio/farmacologia , Compostos de Nitrogênio/toxicidade , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/toxicidade , Pontos Quânticos/química , Pontos Quânticos/toxicidade , Staphylococcus aureus/efeitos dos fármacos , Temperatura
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