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1.
Bull Math Biol ; 86(7): 83, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842602

RESUMO

5-Aminolevulinic Acid (5-ALA) is the only fluorophore approved by the FDA as an intraoperative optical imaging agent for fluorescence-guided surgery in patients with glioblastoma. The dosing regimen is based on rodent tests where a maximum signal occurs around 6 h after drug administration. Here, we construct a computational framework to simulate the transport of 5-ALA through the stomach, blood, and brain, and the subsequent conversion to the fluorescent agent protoporphyrin IX at the tumor site. The framework combines compartmental models with spatially-resolved partial differential equations, enabling one to address questions regarding quantity and timing of 5-ALA administration before surgery. Numerical tests in two spatial dimensions indicate that, for tumors exceeding the detection threshold, the time to peak fluorescent concentration is 2-7 h, broadly consistent with the current surgical guidelines. Moreover, the framework enables one to examine the specific effects of tumor size and location on the required dose and timing of 5-ALA administration before glioblastoma surgery.


Assuntos
Ácido Aminolevulínico , Neoplasias Encefálicas , Simulação por Computador , Glioblastoma , Conceitos Matemáticos , Modelos Biológicos , Protoporfirinas , Cirurgia Assistida por Computador , Glioblastoma/cirurgia , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/diagnóstico por imagem , Ácido Aminolevulínico/administração & dosagem , Humanos , Neoplasias Encefálicas/cirurgia , Protoporfirinas/administração & dosagem , Protoporfirinas/metabolismo , Cirurgia Assistida por Computador/métodos , Animais , Fármacos Fotossensibilizantes/administração & dosagem , Imagem Óptica/métodos , Corantes Fluorescentes/administração & dosagem
2.
Int J Biol Macromol ; 272(Pt 1): 132893, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38838883

RESUMO

Foodborne pathogens result in a great harm to human, which is an urgent problem to be addressed. Herein, a novel cellulose-based packaging films with excellent anti-bacterial properties under visible light were prepared. A porphyrin-based covalent organic polymer (Por-COPs) was constructed, then covalently grafted onto dialdehyde cellulose (DAC). The addition of Por-COPs enhanced the mechanical, hydrophobicity, and water resistance of the DAC-based composite films. DAC/Por-COP-2.5 film exhibited outstanding properties for the photodynamic inactivation of bacteria under visible light irradiation, delivering inactivation efficiencies of 99.90 % and 99.45 % towards Staphylococcus aureus and Escherichia coli within 20 min. The DAC/Por-COPs films efficiently generated •O2- and 1O2 under visible light, thereby causing oxidative stress to cell membranes for bacterial inactivation. The prepared composite film forms a protective barrier against bacterial contamination. Results guide the development of high performance and more sustainable packaging films for the food sector.


Assuntos
Celulose , Escherichia coli , Porfirinas , Staphylococcus aureus , Celulose/química , Celulose/análogos & derivados , Celulose/farmacologia , Porfirinas/química , Porfirinas/farmacologia , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Luz , Embalagem de Alimentos/métodos , Polímeros/química , Polímeros/farmacologia , Esterilização/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia
3.
Nat Commun ; 15(1): 4943, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858372

RESUMO

The development of Type I photosensitizers (PSs) is of great importance due to the inherent hypoxic intolerance of photodynamic therapy (PDT) in the hypoxic microenvironment. Compared to Type II PSs, Type I PSs are less reported due to the absence of a general molecular design strategy. Herein, we report that the combination of typical Type II PS and natural substrate carvacrol (CA) can significantly facilitate the Type I pathway to efficiently generate superoxide radical (O2-•). Detailed mechanism study suggests that CA is activated into thymoquinone (TQ) by local singlet oxygen generated from the PS upon light irradiation. With TQ as an efficient electron transfer mediator, it promotes the conversion of O2 to O2-• by PS via electron transfer-based Type I pathway. Notably, three classical Type II PSs are employed to demonstrate the universality of the proposed approach. The Type I PDT against S. aureus has been demonstrated under hypoxic conditions in vitro. Furthermore, this coupled photodynamic agent exhibits significant bactericidal activity with an antibacterial rate of 99.6% for the bacterial-infection female mice in the in vivo experiments. Here, we show a simple, effective, and universal method to endow traditional Type II PSs with hypoxic tolerance.


Assuntos
Benzoquinonas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Staphylococcus aureus , Benzoquinonas/química , Benzoquinonas/farmacologia , Benzoquinonas/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Animais , Camundongos , Feminino , Fotoquimioterapia/métodos , Transporte de Elétrons/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Cimenos/farmacologia , Cimenos/química , Antibacterianos/farmacologia , Oxigênio Singlete/metabolismo , Superóxidos/metabolismo , Infecções Estafilocócicas/tratamento farmacológico , Humanos , Luz , Camundongos Endogâmicos BALB C
4.
Photodermatol Photoimmunol Photomed ; 40(4): e12978, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38845020

RESUMO

BACKGROUND: Infections are complications in the wound healing process, and their treatment can lead to antibiotic overuse and bacterial resistance. Antimicrobial photodynamic therapy (aPDT) is used to treat infectious diseases caused by fungi, viruses, or bacteria. Methylene blue (MB) and its derivatives are commonly used dyes in antimicrobial photodynamic therapy (aPDT-MB). METHODS: This study is a PRISMA systematic review of animal models used to discuss the usefulness and therapeutic parameters of aPDT-MB or its derivatives for treating infected skin wounds. RESULTS: After an extensive literature review, 13 controlled trials totaling 261 animals were selected to evaluate skin infection by leishmaniasis and cutaneous bacterial and fungal infections. All studies found results favoring the use of aPDT-MB. Great variability in parameters was found for radiant exposure from 12 to 360 J/cm2, MB diluted in saline solution or distilled water, irradiation time from 40 to 3600 s, irradiance most commonly at a maximum of 100 mW/cm2, and wavelength used mainly in the 630-670 nm range. CONCLUSION: MB is a safe and promising agent used as a photosensitizer in aPDT for skin-infected lesions. There is great variability in the parameters found. Comparisons concerning concentration, irradiation time, and light intensity need to be performed.


Assuntos
Azul de Metileno , Fotoquimioterapia , Fármacos Fotossensibilizantes , Animais , Modelos Animais de Doenças , Azul de Metileno/farmacologia , Azul de Metileno/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico
5.
J Refract Surg ; 40(6): e392-e397, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38848056

RESUMO

PURPOSE: To compare the effects of corneal allogenic intrastromal ring segment (CAIRS) implantation on topographical measurements and visual outcomes of patients with keratoconus with and without corneal cross-linking (CXL) prior to the time of implantation. METHODS: Sixty-seven eyes with corneal allograft intrastromal ring segment implantation (KeraNatural; Lions VisionGift) due to advanced keratoconus were included in the study. Thirty-seven eyes had no CXL and 30 eyes had had CXL before being referred to the authors. The changes in spherical equivalent (SE), uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), steep keratometry (K1), flat keratometry (K2), mean keratometry (Kmean), maximum keratometry (Kmax), and thinnest pachymetry were retrospectively analyzed 6 months after the implantation. RESULTS: The median age was 29 years in the CXL group and 24.0 years in the non-CXL group (P > .05), respectively. All topographical and visual parameters before implantation were similar in both groups (P > .05 for all parameters). At 6 months, CDVA, K1, and Kmean showed higher improvement in the non-CXL group than the CXL group (P = .030, .018, and .039, respectively). CONCLUSIONS: CAIRS surgery has a flattening effect on both the corneas with and without CXL. The cornea with prior CXL treatment had less flattening effect due to the stiffening effect of prior CXL. [J Refract Surg. 2024;40(6):e392-e397.].


Assuntos
Colágeno , Substância Própria , Topografia da Córnea , Reagentes de Ligações Cruzadas , Ceratocone , Fármacos Fotossensibilizantes , Próteses e Implantes , Implantação de Prótese , Refração Ocular , Acuidade Visual , Humanos , Ceratocone/fisiopatologia , Ceratocone/metabolismo , Ceratocone/tratamento farmacológico , Ceratocone/cirurgia , Substância Própria/metabolismo , Substância Própria/cirurgia , Reagentes de Ligações Cruzadas/uso terapêutico , Acuidade Visual/fisiologia , Adulto , Masculino , Feminino , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Retrospectivos , Adulto Jovem , Refração Ocular/fisiologia , Colágeno/metabolismo , Paquimetria Corneana , Riboflavina/uso terapêutico , Fotoquimioterapia/métodos , Adolescente , Raios Ultravioleta , Transplante de Córnea/métodos , Pessoa de Meia-Idade , Crosslinking Corneano
6.
Lasers Med Sci ; 39(1): 151, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839711

RESUMO

The aim of this study was to compare two types of light irradiation devices for antimicrobial photodynamic therapy (aPDT). A 660-nm light-emitting diode (LED) and a 665-nm laser diode (LD) were used for light irradiation, and 0.1 mg/L TONS 504, a cationic chlorin derivative, was used as the photosensitizer. We evaluated the light attenuation along the vertical and horizontal directions, temperature rise following light irradiation, and aPDT efficacy against Staphylococcus aureus under different conditions: TONS 504 only, light irradiation only, and TONS 504 with either LED (30 J/cm2) or LD light irradiation (continuous: 30 J/cm2; pulsed: 20 J/cm2 at 2/3 duty cycle, 10 J/cm2 at 1/3 duty cycle). Both LED and LD light intensities were inversely proportional to the square of the vertical distance from the irradiated area. Along the horizontal distance from the nadir of the light source, the LED light intensity attenuated according to the cosine quadrature law, while the LD light intensity did not attenuate within the measurable range. Following light irradiation, the temperature rise increased as the TONS 504 concentration increased in the order of pulsed LD < continuous LD < LED irradiation. aPDT with light irradiation only or TONS 504 only had no antimicrobial effect, while aPDT with TONS 504 under continuous or pulsed LD light irradiation provided approximately 3 log reduction at 30 J/cm2 and 20 J/cm2 and approximately 2 log reduction at 10 J/cm2. TONS 504-aPDT under pulsed LD light irradiation provided anti-microbial effect without significant temperature rise.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Staphylococcus aureus , Fotoquimioterapia/métodos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/efeitos da radiação , Fármacos Fotossensibilizantes/farmacologia , Humanos , Lasers Semicondutores/uso terapêutico , Porfirinas/farmacologia , Temperatura
7.
Planta Med ; 90(7-08): 588-594, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38843798

RESUMO

Antimicrobial photodynamic therapy (aPDT) is an evolving treatment strategy against human pathogenic microbes such as the Candida species, including the emerging pathogen C. auris. Using a modified EUCAST protocol, the light-enhanced antifungal activity of the natural compound parietin was explored. The photoactivity was evaluated against three separate strains of five yeasts, and its molecular mode of action was analysed via several techniques, i.e., cellular uptake, reactive electrophilic species (RES), and singlet oxygen yield. Under experimental conditions (λ = 428 nm, H = 30 J/cm2, PI = 30 min), microbial growth was inhibited by more than 90% at parietin concentrations as low as c = 0.156 mg/L (0.55 µM) for C. tropicalis and Cryptococcus neoformans, c = 0.313 mg/L (1.10 µM) for C. auris, c = 0.625 mg/L (2.20 µM) for C. glabrata, and c = 1.250 mg/L (4.40 µM) for C. albicans. Mode-of-action analysis demonstrated fungicidal activity. Parietin targets the cell membrane and induces cell death via ROS-mediated lipid peroxidation after light irradiation. In summary, parietin exhibits light-enhanced fungicidal activity against all Candida species tested (including C. auris) and Cryptococcus neoformans, covering three of the four critical threats on the WHO's most recent fungal priority list.


Assuntos
Antifúngicos , Cryptococcus neoformans , Testes de Sensibilidade Microbiana , Antifúngicos/farmacologia , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/efeitos da radiação , Candida auris/efeitos dos fármacos , Luz , Candida/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fotoquimioterapia/métodos , Antraquinonas/farmacologia , Fármacos Fotossensibilizantes/farmacologia
8.
Inorg Chem ; 63(24): 11450-11458, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38823006

RESUMO

Two Ru(II) complexes, [Ru(pydppn)(bim)(py)]2+ [2; pydppn = 3-(pyrid-2'-yl)-4,5,9,16-tetraaza-dibenzo[a,c]naphthacene; bim = 2,2'-bisimidazole; py = pyridine] and [Ru(pydppn)(Me4bim)(py)]2+ [3; Me4bim = 2,2'-bis(4,5-dimethylimidazole)], were synthesized and characterized, and their photophysical properties, DNA binding, and photocleavage were evaluated and compared to [Ru(pydppn)(bpy)(py)]2+ (1; bpy = 2,2'-bipyridine). Complexes 2 and 3 exhibit broad 1MLCT (metal-to-ligand charge transfer) transitions with maxima at ∼470 nm and shoulders at ∼525 and ∼600 nm that extend to ∼800 nm. These bands are red-shifted relative to those of 1, attributed to the π-donating ability of the bim and Me4bim ligands. A strong signal at 550 nm is observed in the transient absorption spectra of 1-3, previously assigned as arising from a pydppn-centered 3ππ* state, with lifetimes of ∼19 µs for 1 and 2 and ∼270 ns for 3. A number of methods were used to characterize the mode of binding of 1-3 to DNA, including absorption titrations, thermal denaturation, relative viscosity changes, and circular dichroism, all of which point to the intercalation of the pydpppn ligand between the nucleobases. The photocleavage of plasmid pUC19 DNA was observed upon the irradiation of 1-3 with visible and red light, attributed to the sensitized generation of 1O2 by the complexes. These findings indicate that the bim ligand, together with pydppn, serves to shift the absorption of Ru(II) complexes to the photodynamic therapy window, 600-900 nm, and also extend the excited state lifetimes for the efficient production of cytotoxic singlet oxygen.


Assuntos
Complexos de Coordenação , DNA , Fotoquimioterapia , Fármacos Fotossensibilizantes , Plasmídeos , Rutênio , Oxigênio Singlete , DNA/química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/efeitos da radiação , Rutênio/química , Rutênio/farmacologia , Plasmídeos/química , Oxigênio Singlete/metabolismo , Oxigênio Singlete/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Estrutura Molecular , Clivagem do DNA/efeitos dos fármacos , Clivagem do DNA/efeitos da radiação
9.
ACS Appl Bio Mater ; 7(6): 3731-3745, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38842103

RESUMO

Photosensitizing agents have received increased attention from the medical community, owing to their higher photothermal efficiency, induction of hyperthermia, and sustained delivery of bioactive molecules to their targets. Micro/nanorobots can be used as ideal photosensitizing agents by utilizing various physical stimuli for the targeted killing of pathogens (e.g., bacteria) and cancer cells. Herein, we report sunflower-pollen-inspired spiky zinc oxide (s-ZnO)-based nanorobots that effectively kill bacteria and cancer cells under near-infrared (NIR) light irradiation. The as-fabricated s-ZnO was modified with a catechol-containing photothermal agent, polydopamine (PDA), to improve its NIR-responsive properties, followed by the addition of antimicrobial (e.g., tetracycline/TCN) and anticancer (e.g., doxorubicin/DOX) drugs. The fabricated s-ZnO/PDA@Drug nanobots exhibited unique locomotory behavior with an average speed ranging from 13 to 14 µm/s under 2.0 W/cm2 NIR light irradiation. Moreover, the s-ZnO/PDA@TCN nanobots exhibited superior antibacterial activity against E. coli and S. epidermidis under NIR irradiation. The s-ZnO/PDA@DOX nanobots also displayed sufficient reactive oxygen species (ROS) amplification in B16F10 melanoma cells and induced apoptosis under NIR light, indicating their therapeutic efficacy. We hope the sunflower pollen-inspired s-ZnO nanorobots have tremendous potential in biomedical engineering from the phototherapy perspective, with the hope to reduce pathogen infections.


Assuntos
Antibacterianos , Antineoplásicos , Materiais Biocompatíveis , Ensaios de Seleção de Medicamentos Antitumorais , Helianthus , Tamanho da Partícula , Fármacos Fotossensibilizantes , Óxido de Zinco , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Helianthus/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Teste de Materiais , Testes de Sensibilidade Microbiana , Pólen/química , Escherichia coli/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Indóis/química , Indóis/farmacologia , Animais , Camundongos , Doxorrubicina/farmacologia , Doxorrubicina/química , Raios Infravermelhos
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 319: 124529, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38824758

RESUMO

Considering the increasing number of pathogens resistant to commonly used antibiotics as well as antiseptics, there is an urgent need for antimicrobial approaches that can effectively inactivate pathogens without the risk of establishing resistance. An alternative approach in this context is antibacterial photodynamic therapy (APDT). APDT is a process that involves bacterial cell death using appropriate wavelength light energy and photosensitizer and causes the production of reactive oxygen species inside or outside the microbial cell depending on the penetration of light energy. In our study, a new porphyrin compound 4,4'-methylenebis(2-((E)-((4-(10,15,20-triphenylporphyrin-5-yl)phenyl)imino)methyl)phenol) (SP) was designed and synthesized as photosensitizer and its structure was clarified by NMR (13C and 1H) and mass determination method. Photophysical and photochemical properties were examined in detail using different methods. Singlet oxygen quantum yields were obtained as 0.48 and 0.59 by direct and indirect methods, respectively. Antibacterial activity studies have been conducted within the scope of biological activity and promising results have been obtained under LED light (500-700 nm, 265 V, 1500 LM), contributing to the antibacterial photodynamic therapy literature.


Assuntos
Antibacterianos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Porfirinas , Oxigênio Singlete , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/síntese química , Porfirinas/química , Porfirinas/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Oxigênio Singlete/metabolismo , Oxigênio Singlete/química , Testes de Sensibilidade Microbiana , Luz , Bactérias/efeitos dos fármacos , Desenho de Fármacos
11.
Int J Mol Sci ; 25(11)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38891819

RESUMO

Photothermal therapy (PTT) is a promising cancer therapy modality with significant advantages such as precise targeting, convenient drug delivery, better efficacy, and minimal adverse effects. Photothermal therapy effectively absorbs the photothermal transducers in the near-infrared region (NIR), which induces the photothermal effect to work. Although PTT has a better role in tumor therapy, it also suffers from low photothermal conversion efficiency, biosafety, and incomplete tumor elimination. Therefore, the use of nanomaterials themselves as photosensitizers, the targeted modification of nanomaterials to improve targeting efficiency, or the combined use of nanomaterials with other therapies can improve the therapeutic effects and reduce side effects. Notably, noble metal nanomaterials have attracted much attention in PTT because they have strong surface plasmon resonance and an effective absorbance light at specific near-infrared wavelengths. Therefore, they can be used as excellent photosensitizers to mediate photothermal conversion and improve its efficiency. This paper provides a comprehensive review of the key role played by noble metal nanomaterials in tumor photothermal therapy. It also describes the major challenges encountered during the implementation of photothermal therapy.


Assuntos
Nanopartículas Metálicas , Neoplasias , Terapia Fototérmica , Humanos , Terapia Fototérmica/métodos , Neoplasias/terapia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Animais , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico
12.
Int J Mol Sci ; 25(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38891885

RESUMO

Anti-tumor photodynamic therapy (PDT) is a unique modality that employs a photosensitizer (PS), PS-exciting light, and O2 to generate cytotoxic oxidants. For various reasons, not all malignant cells in any given tumor will succumb to a PDT challenge. Previous studies by the authors revealed that nitric oxide (NO) from inducible NO synthase (iNOS/NOS2) plays a key role in tumor cell resistance and also stimulation of migratory/invasive aggressiveness of surviving cells. iNOS was the only NOS isoform implicated in these effects. Significantly, NO from stress-upregulated iNOS was much more important in this regard than NO from preexisting enzymes. Greater NO-dependent resistance, migration, and invasion was observed with at least three different cancer cell lines, and this was attenuated by iNOS activity inhibitors, NO scavengers, or an iNOS transcriptional inhibitor. NO diffusing from PDT-targeted cells also stimulated migration/invasion potency of non-targeted bystander cells. Unless counteracted by appropriate measures, all these effects could seriously compromise clinical PDT efficacy. Here, we will review specific examples of these negative side effects of PDT and how they might be suppressed by adjuvants such as NO scavengers or inhibitors of iNOS activity or expression.


Assuntos
Movimento Celular , Invasividade Neoplásica , Neoplasias , Óxido Nítrico Sintase Tipo II , Óxido Nítrico , Fotoquimioterapia , Humanos , Óxido Nítrico Sintase Tipo II/metabolismo , Movimento Celular/efeitos dos fármacos , Óxido Nítrico/metabolismo , Fotoquimioterapia/métodos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Animais , Regulação para Cima/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia
13.
Int J Mol Sci ; 25(11)2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38892328

RESUMO

Curcumin is a natural compound that is considered safe and may have potential health benefits; however, its poor stability and water insolubility limit its therapeutic applications. Different strategies aim to increase its water solubility. Here, we tested the compound PVP-curcumin as a photosensitizer for antimicrobial photodynamic therapy (aPDT) as well as its potential to act as an adjuvant in antibiotic drug therapy. Gram-negative E. coli K12 and Gram-positive S. capitis were subjected to aPDT using various PVP-curcumin concentrations (1-200 µg/mL) and 475 nm blue light (7.5-45 J/cm2). Additionally, results were compared to aPDT using 415 nm blue light. Gene expression of recA and umuC were analyzed via RT-qPCR to assess effects on the bacterial SOS response. Further, the potentiation of Ciprofloxacin by PVP-curcumin was investigated, as well as its potential to prevent the emergence of antibiotic resistance. Both bacterial strains were efficiently reduced when irradiated with 415 nm blue light (2.2 J/cm2) and 10 µg/mL curcumin. Using 475 nm blue light, bacterial reduction followed a biphasic effect with higher efficacy in S. capitis compared to E. coli K12. PVP-curcumin decreased recA expression but had limited effect regarding enhancing antibiotic treatment or impeding resistance development. PVP-curcumin demonstrated effectiveness as a photosensitizer against both Gram-positive and Gram-negative bacteria but did not modulate the bacterial SOS response.


Assuntos
Antibacterianos , Ciprofloxacina , Curcumina , Fármacos Fotossensibilizantes , Recombinases Rec A , Curcumina/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Recombinases Rec A/metabolismo , Recombinases Rec A/genética , Ciprofloxacina/farmacologia , Antibacterianos/farmacologia , Fotoquimioterapia/métodos , Resposta SOS em Genética/efeitos dos fármacos , Escherichia coli K12/efeitos dos fármacos , Escherichia coli K12/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Povidona/química , Povidona/farmacologia , Testes de Sensibilidade Microbiana , Escherichia coli/efeitos dos fármacos , Luz , Proteínas de Ligação a DNA
14.
Molecules ; 29(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38893346

RESUMO

Photosensitizers cause oxidative damages in various biological systems under light. In this study, the method for analyzing photosensitizing activity of various dietary and medicinal sources was developed using 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (thiazolyl blue formazan; MTT-F) as a probe. Significant and quantitative decolorization of MTT-F was observed in the presence of photosensitizers used in this study under light but not under dark conditions. The decolorization of MTT-F occurred irradiation time-, light intensity-, and photosensitizer concentration-dependently. The decolorized MTT-F was reversibly reduced by living cells; the LC-MS/MS results indicated the formation of oxidized products with -1 m/z of base peak from MTT-F, suggesting that MTT-F decolorized by photosensitizers was its corresponding tetrazolium. The present results indicate that MTT-F is a reliable probe for the quantitative analysis of photosensitizing activities, and the MTT-F-based method can be an useful tool for screening and evaluating photosensitizing properties of various compounds used in many industrial purposes.


Assuntos
Formazans , Fármacos Fotossensibilizantes , Sais de Tetrazólio , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Humanos , Sais de Tetrazólio/química , Formazans/química , Espectrometria de Massas em Tandem/métodos , Tiazóis/química , Luz , Cromatografia Líquida/métodos , Corantes/química
15.
ACS Macro Lett ; 13(6): 768-774, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38829688

RESUMO

The low therapeutic efficacy and potential long-term toxicity of antitumor treatments seriously limit the clinical application of phototherapies. Herein, we develop a degradable phototheranostic nanoplatform for NIR-II fluorescence bioimaging-guided synergistic photothermal (PTT) and photodynamic therapies (PDT) and immune activation to inhibit tumor growth. The phototheranostic nanoplatform (CX@PSS) consists of multidisulfide-containing polyurethane loaded with a photosensitizer CX, which can be specifically degraded in the GSH overexpressed tumor microenvironment (TME) and exhibits good NIR-II fluorescence, photodynamic, and photothermal properties. Under 808 nm light irradiation, CX@PSS exhibits efficient photothermal conversion and ROS generation, which further induces immunogenic cell death (ICD), releasing tumor-associated antigens and activating the immune response. In vitro and in vivo studies confirm the potential of CX@PSS in NIR II FL imaging-guided tumor treatments by synergistic PTT, PDT, and immune activation. This work is expected to provide a new pathway for clinical applications of imaging-guided tumor diagnosis and treatments.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Nanomedicina Teranóstica , Microambiente Tumoral , Microambiente Tumoral/efeitos dos fármacos , Animais , Camundongos , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Nanomedicina Teranóstica/métodos , Fotoquimioterapia/métodos , Imagem Óptica/métodos , Raios Infravermelhos , Nanopartículas/química , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral , Neoplasias/diagnóstico por imagem , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Terapia Fototérmica/métodos , Poliuretanos/química , Poliuretanos/farmacologia
16.
Int J Nanomedicine ; 19: 5837-5858, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887692

RESUMO

Purpose: Phototherapy, known for its high selectivity, few side effects, strong controllability, and synergistic enhancement of combined treatments, is widely used in treating diseases like cervical cancer. Methods: In this study, hollow mesoporous manganese dioxide was used as a carrier to construct positively charged, poly(allylamine hydrochloride)-modified nanoparticles (NPs). The NP was efficiently loaded with the photosensitizer indocyanine green (ICG) via the addition of hydrogen phosphate ions to produce a counterion aggregation effect. HeLa cell membrane encapsulation was performed to achieve the final M-HMnO2@ICG NP. In this structure, the HMnO2 carrier responsively degrades to release ICG in the tumor microenvironment, self-generates O2 for sensitization to ICG-mediated photodynamic therapy (PDT), and consumes GSH to expand the oxidative stress therapeutic effect [chemodynamic therapy (CDT) + PDT]. The ICG accumulated in tumor tissues exerts a synergistic PDT/photothermal therapy (PTT) effect through single laser irradiation, improving efficiency and reducing side effects. The cell membrane encapsulation increases nanomedicine accumulation in tumor tissues and confers an immune evasion ability. In addition, high local temperatures induced by PTT can enhance CDT. These properties of the NP enable full achievement of PTT/PDT/CDT and targeted effects. Results: Mn2+ can serve as a magnetic resonance imaging agent to guide therapy, and ICG can be used for photothermal and fluorescence imaging. After its intravenous injection, M-HMnO2@ICG accumulated effectively at mouse tumor sites; the optimal timing of in-vivo laser treatment could be verified by near-infrared fluorescence, magnetic resonance, and photothermal imaging. The M-HMnO2@ICG NPs had the best antitumor effects among treatment groups under near-infrared light conditions, and showed good biocompatibility. Conclusion: In this study, we designed a nano-biomimetic delivery system that improves hypoxia, responds to the tumor microenvironment, and efficiently loads ICG. It provides a new economical and convenient strategy for synergistic phototherapy and CDT for cervical cancer.


Assuntos
Verde de Indocianina , Compostos de Manganês , Imagem Multimodal , Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Microambiente Tumoral , Neoplasias do Colo do Útero , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/tratamento farmacológico , Feminino , Microambiente Tumoral/efeitos dos fármacos , Humanos , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Fotoquimioterapia/métodos , Animais , Células HeLa , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Nanopartículas/química , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Camundongos , Imagem Multimodal/métodos , Terapia Fototérmica/métodos , Óxidos/química , Óxidos/farmacologia , Camundongos Endogâmicos BALB C , Poliaminas/química , Poliaminas/farmacologia , Imageamento por Ressonância Magnética/métodos
17.
J Dermatolog Treat ; 35(1): 2368066, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38897607

RESUMO

PURPOSE: To evaluate the efficacy of Mohs micrographic surgery (MMS) combined with photodynamic therapy (PDT) in treating non-invasive extramammary Paget's disease (EMPD). MATERIALS AND METHODS: A 77-year-old male patient with non-invasive EMPD was treated with MMS followed by PDT. Preoperative fluorescence localization using 5-aminolevulinic acid (ALA) was performed to determine the surgical scope. MMS was conducted under lumbar anesthesia with intraoperative frozen-section pathology. Postoperative PDT was administered weekly for three sessions. RESULTS: The patient achieved negative surgical margins after two rounds of intraoperative pathology. Postoperative follow-up over two years showed no recurrence, and the patient did not experience significant adverse reactions. CONCLUSION: The combination of MMS and PDT was effective in treating non-invasive EMPD, demonstrating favorable clinical outcomes and no recurrence over the two-year follow-up period.


Assuntos
Ácido Aminolevulínico , Cirurgia de Mohs , Doença de Paget Extramamária , Fotoquimioterapia , Fármacos Fotossensibilizantes , Neoplasias Cutâneas , Humanos , Masculino , Idoso , Doença de Paget Extramamária/patologia , Doença de Paget Extramamária/tratamento farmacológico , Doença de Paget Extramamária/cirurgia , Ácido Aminolevulínico/uso terapêutico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/terapia , Fármacos Fotossensibilizantes/uso terapêutico , Resultado do Tratamento , Terapia Combinada , Margens de Excisão
18.
J Nanobiotechnology ; 22(1): 348, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898486

RESUMO

Tumor-associated macrophages (TAMs) are a promising target for cancer immunotherapy, but delivering therapeutic agents to TAMs within the tumor microenvironment (TME) is challenging. In this study, a photosensitive, dual-targeting nanoparticle system (M.RGD@Cr-CTS-siYTHDF1 NPs) was developed. The structure includes a shell of DSPE-modified RGD peptides targeting integrin receptors on tumor cells and carboxymethyl mannose targeting CD206 receptors on macrophages, with a core of chitosan adsorbing m6A reading protein YTHDF1 siRNA and chromium nanoparticles (Cr NPs). The approach is specifically designed to target TAM and cancer cells, utilizing the photothermal effect of Cr NPs to disrupt the TME and deliver siYTHDF1 to TAM. In experiments with tumor-bearing mice, M.RGD@Cr-CTS-siYTHDF1 NPs, when exposed to laser irradiation, effectively killed tumor cells, disrupted the TME, delivered siYTHDF1 to TAMs, silenced the YTHDF1 gene, and shifted the STAT3-STAT1 equilibrium by reducing STAT3 and enhancing STAT1 expression. This reprogramming of TAMs towards an anti-tumor phenotype led to a pro-immunogenic TME state. The strategy also suppressed immunosuppressive IL-10 production, increased expression of immunostimulatory factors (IL-12 and IFN-γ), boosted CD8 + T cell infiltration and M1-type TAMs, and reduced Tregs and M2-type TAMs within the TME. In conclusion, the dual-targeting M.RGD@Cr-CTS-siYTHDF1 NPs, integrating dual-targeting capabilities with photothermal therapy (PTT) and RNA interference, offer a promising approach for molecular targeted cancer immunotherapy with potential for clinical application.


Assuntos
Imunoterapia , Neoplasias Hepáticas , RNA Interferente Pequeno , Animais , Camundongos , Imunoterapia/métodos , Humanos , Neoplasias Hepáticas/terapia , Linhagem Celular Tumoral , Microambiente Tumoral , Macrófagos Associados a Tumor/metabolismo , Proteínas de Ligação a RNA/metabolismo , Nanopartículas/química , Nanopartículas Metálicas/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química
19.
Int J Nanomedicine ; 19: 5637-5680, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38882538

RESUMO

Photodynamic therapy (PDT) is a non-invasive therapy that has made significant progress in treating different diseases, including cancer, by utilizing new nanotechnology products such as graphene and its derivatives. Graphene-based materials have large surface area and photothermal effects thereby making them suitable candidates for PDT or photo-active drug carriers. The remarkable photophysical properties of graphene derivates facilitate the efficient generation of reactive oxygen species (ROS) upon light irradiation, which destroys cancer cells. Surface functionalization of graphene and its materials can also enhance their biocompatibility and anticancer activity. The paper delves into the distinct roles played by graphene-based materials in PDT such as photosensitizers (PS) and drug carriers while at the same time considers how these materials could be used to circumvent cancer resistance. This will provide readers with an extensive discussion of various pathways contributing to PDT inefficiency. Consequently, this comprehensive review underscores the vital roles that graphene and its derivatives may play in emerging PDT strategies for cancer treatment and other medical purposes. With a better comprehension of the current state of research and the existing challenges, the integration of graphene-based materials in PDT holds great promise for developing targeted, effective, and personalized cancer treatments.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Grafite , Neoplasias , Fotoquimioterapia , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio , Grafite/química , Grafite/farmacologia , Fotoquimioterapia/métodos , Humanos , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Portadores de Fármacos/química , Animais
20.
Int J Nanomedicine ; 19: 4679-4699, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38803997

RESUMO

Background: Breast cancer is a heterogeneous disease globally accounting for approximately 1 million new cases annually. Chemotherapy remains the main therapeutic option, but the antitumor efficacy needs to be improved. Methods: Two multifunctional nanoparticles were developed in this paper using oleic acid and mPEG2k-PCL2k as the drug carriers. Squamocin (Squ) was employed as a chemotherapeutic agent. Resiquimod (R848) or ginsenoside Rh2 was co-encapsulated in the nanoparticles to remold the immunosuppressive tumor microenvironment, and IR780 was coloaded as a photosensitizer to realize photothermal therapy. Results: The obtained Squ-R848-IR780 nanoparticles and Squ-Rh2-IR780 nanoparticles were uniformly spherical and approximately (162.200 ± 2.800) nm and (157.300 ± 1.1590) nm, respectively, in average diameter, with good encapsulation efficiency (above 85% for each drug), excellent stability in various physiological media and high photothermal conversion efficiency (24.10% and 22.58%, respectively). After intravenous administration, both nanoparticles quickly accumulated in the tumor and effectively enhanced the local temperature of the tumor to over 45 °C when irradiated by an 808 nm laser. At a low dose of 0.1 mg/kg, Squ nanoparticles treatment alone displayed a tumor inhibition rate of 55.28%, pulmonary metastasis inhibition rate of 59.47% and a mean survival time of 38 days, which were all higher than those of PTX injection (8 mg/kg) (43.64%, 25 days and 37.25%), indicating that Squ was a potent and effective antitumor agent. Both multifunctional nanoparticles, Squ-Rh2-IR780 nanoparticles and Squ-R848-IR780 nanoparticles, demonstrated even better therapeutic efficacy, with tumor inhibition rates of 90.02% and 97.28%, pulmonary metastasis inhibition rates of 95.42% and 98.09, and mean survival times of 46 days and 52 days, respectively. Conclusion: The multifunctional nanoparticles coloaded with squamocin, R848 and IR 780 achieved extraordinary therapeutic efficacy and excellent antimetastasis activity and are thus promising in the future treatment of breast tumors and probably other tumors.


Assuntos
Neoplasias da Mama , Indóis , Nanopartículas , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Animais , Nanopartículas/química , Humanos , Indóis/química , Indóis/farmacologia , Linhagem Celular Tumoral , Camundongos , Portadores de Fármacos/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Terapia Fototérmica/métodos , Camundongos Endogâmicos BALB C , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/administração & dosagem , Imidazóis/química , Imidazóis/farmacologia , Imidazóis/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Microambiente Tumoral/efeitos dos fármacos
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