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1.
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
2.
Lasers Med Sci ; 39(1): 155, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865020

RESUMO

The aim of this systematic review and meta-analysis (SRM) was to evaluate the effectiveness of the adjunctive use of antimicrobial photodynamic therapy (aPDT) in non-surgical periodontal treatment (NSPT) in subjects with Human Immunodeficiency Virus (HIV) and periodontitis. This SRM was registered in PROSPERO (CRD42023410180) and followed the guidelines of PRISMA 2020. Searches were performed in different electronic databases. Risk of bias was performed using the Cochrane Risk of Bias tool (RoB 2.0) for randomized clinical trials (RCT). Meta-analysis was performed using Rev Man software. The mean difference (MD) measure of effect was calculated, the random effect model was applied with a 95% confidence interval, and heterogeneity was tested by the I2 index. The certainty of the evidence was rated using GRADE. A total of 1118 records were screened, and four studies were included. There was a greater reduction in the microbial load of periodontopathogens after NSPT with aPDT. Meta-analysis showed that probing depth (post 3 and 6 months) and clinical attachment loss (post 6 months) were lower for the aPDT-treated group than the NSPT alone: MD -0.39 [-0.74; -0.05], p = 0.02; MD -0.70 [-0.99; -0.41], p < 0.0001; MD -0.84 [-1,34; -0.34], p = 0.0001, respectively. Overall, the studies had a low risk of bias and, the certainty of evidence was rated as moderate. It is suggested that aPDT is a promising adjuvant therapy, showing efficacy in the reduction of the microbial load and in some clinical parameters of individuals with periodontitis and HIV.


Assuntos
Infecções por HIV , Periodontite , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Periodontite/terapia , Periodontite/tratamento farmacológico , Periodontite/microbiologia , Anti-Infecciosos/uso terapêutico , Anti-Infecciosos/administração & dosagem
3.
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
4.
F1000Res ; 13: 152, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38854440

RESUMO

Background: Managing recalcitrant oral lichen planus (OLP) can be challenging. Laser therapy has been suggested as an alternative to corticosteroids for treatment. Photodynamic therapy (PDT) is a non-invasive technique that enables the removal of lesions without surgery. Photobiomodulation therapy (PBMT) can promote healing and recovery of the lesions. Case presentation: The objective was to treat unresponsive bilateral OLP of the whole buccal mucosae with a combination of PDT and PBMT. Results: A 43-year-old Thai male presented with the severe painful reticular type of OLP of bilateral buccal mucosae involving upper and lower vestibular areas. The lesions were not remitted with either prednisolone systemic steroids or fluocinolone topical corticosteroids. After undergoing ten sessions of PDT with 10% 5-Aminolevulinic acid (5-ALA) in the form of thermoplastic gel and a 635 nm diode laser at 100 to 400 mW with an energy density of 20 to 30 J/cm 2 in continuous wave mode, combined with five interim-sessions of PBMT using a 635 nm diode laser at 200 to 300 mW with an energy density of 6 to 10 J/cm 2 in continuous wave, the patient reported relief of burning sensation beside remission of lesions without any complications. Conclusion: The wide-spreading recalcitrant OLP with burning sensation can be managed by combining PDT and PBMT.


Assuntos
Líquen Plano Bucal , Terapia com Luz de Baixa Intensidade , Mucosa Bucal , Fotoquimioterapia , Humanos , Masculino , Adulto , Fotoquimioterapia/métodos , Líquen Plano Bucal/tratamento farmacológico , Líquen Plano Bucal/terapia , Líquen Plano Bucal/radioterapia , Líquen Plano Bucal/patologia , Mucosa Bucal/patologia , Terapia com Luz de Baixa Intensidade/métodos , Terapia Combinada , Ácido Aminolevulínico/uso terapêutico , Ácido Aminolevulínico/análogos & derivados
5.
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
6.
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
7.
J Nanobiotechnology ; 22(1): 313, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840120

RESUMO

Adoptive cellular immunotherapy as a promising and alternative cancer therapy platform is critical for future clinical applications. Natural killer (NK) cells have attracted attention as an important type of innate immune regulatory cells that can rapidly kill multiple adjacent cancer cells. However, these cells are significantly less effective in treating solid tumors than in treating hematological tumors. Herein, we report the synthesis of a Fe3O4-PEG-CD56/Avastin@Ce6 nanoprobe labeled with NK-92 cells that can be used for adoptive cellular immunotherapy, photodynamic therapy and dual-modality imaging-based in vivo fate tracking. The labeled NK-92 cells specifically target the tumor cells, which increases the amount of cancer cell apoptosis in vitro. Furthermore, the in vivo results indicate that the labeled NK-92 cells can be used for tumor magnetic resonance imaging and fluorescence imaging, adoptive cellular immunotherapy, and photodynamic therapy after tail vein injection. These data show that the developed multifunctional nanostructure is a promising platform for efficient innate immunotherapy, photodynamic treatment and noninvasive therapeutic evaluation of breast cancer.


Assuntos
Neoplasias da Mama , Antígeno CD56 , Células Matadoras Naturais , Fotoquimioterapia , Polietilenoglicóis , Neoplasias da Mama/terapia , Humanos , Feminino , Animais , Fotoquimioterapia/métodos , Camundongos , Polietilenoglicóis/química , Linhagem Celular Tumoral , Antígeno CD56/metabolismo , Imunoterapia Adotiva/métodos , Apoptose/efeitos dos fármacos , Imageamento por Ressonância Magnética/métodos , Camundongos Endogâmicos BALB C , Camundongos Nus
8.
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
9.
Artif Cells Nanomed Biotechnol ; 52(1): 309-320, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38781462

RESUMO

Photodynamic therapy (PDT) holds great potential to overcome limitations associated with common colorectal cancer (CRC) treatment approaches. Targeted photosensitiser (PS) delivery systems using nanoparticles (NPs) with targeting moieties are continually being designed, which are aimed at enhancing PS efficacy in CRC PDT. However, the optimisation of targeted PS delivery systems in most, in vitro PDT studies has been conducted on two dimensional (2D) monolayers cell cultures. In our present study, we developed a nano PS delivery system for in vitro cultured human colorectal three-dimensional multicellular spheroids (3D MCTS). PEGylated gold nanoparticles (PEG-AuNPs) were prepared and attached to ZnPcS4PS and further functionalised with specific CRC targeting anti-Guanylate Cyclase monoclonal antibodies(mAb). The ZnPcS4-AuNP-Anti-GCC Ab (BNC) nanoconjugates were successfully synthesised and their photodynamic effect investigated following exposure to laser irradiation and demonstrated enhanced anticancer effects in Caco-2 cells cultivated as 3D MCTS spheroids. Our findings suggest that targeted BNC nanoconjugates can improve the efficacy of PDT and highlight the potential of 3D MCTS tumour model for evaluating of targeted PDT.


Assuntos
Neoplasias Colorretais , Ouro , Nanopartículas Metálicas , Fotoquimioterapia , Esferoides Celulares , Humanos , Ouro/química , Ouro/farmacologia , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/patologia , Esferoides Celulares/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Nanopartículas Metálicas/química , Células CACO-2 , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Polietilenoglicóis/química
10.
Lasers Med Sci ; 39(1): 135, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787412

RESUMO

In this study, we assess the impact of photodynamic therapy (PDT) using aluminum phthalocyanine tetrasulfonate (AlPcS4) on the viability and cellular stress responses of MCF-7 breast cancer cells. Specifically, we investigate changes in cell viability, cytokine production, and the expression of stress-related genes. Experimental groups included control cells, those treated with AlPcS4 only, light-emitting diode (LED) only, and combined PDT. To evaluate these effects on cell viability, cytokine production, and the expression of stress-related genes, techniques such as 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, enzyme-linked immunosorbent assays (ELISA), and real-time quantitative PCR (RT‒qPCR) were employed. Our findings reveal how PDT with AlPcS4 modulates mitochondrial activity and cytokine responses, shedding light on the cellular pathways essential for cell survival and stress adaptation. This work enhances our understanding of PDT's therapeutic potential and mechanisms in treating breast cancer.


Assuntos
Neoplasias da Mama , Sobrevivência Celular , Citocinas , Indóis , Compostos Organometálicos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Humanos , Fotoquimioterapia/métodos , Células MCF-7 , Citocinas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Compostos Organometálicos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Indóis/farmacologia , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Ensaio de Imunoadsorção Enzimática
11.
Photodiagnosis Photodyn Ther ; 45: 103869, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38787766

RESUMO

BACKGROUND: For malignant glioma, intraoperative photodynamic therapy (PDT) using talaporfin sodium is a powerful tool for local tumor control, when gross total removal is performed. However, the efficacy of PDT for non-totally resectable malignant glioma has not been clearly confirmed. Therefore, the purpose of this study was to clarify the usefulness of PDT using talaporfin sodium for non-totally resectable malignant glioma. METHODS: Eighteen patients with malignant glioma (16 new onset, 2 recurrent) in whom gross total removal was judged to be difficult from the images obtained before surgery were evaluated. Fifteen patients had glioblastoma (14 newly diagnosed, 1 recurrent), and 3 patients had anaplastic oligodendroglioma (2 newly diagnosed, 1 recurrent). The whole resection cavity was subjected to PDT during the surgery. For newly diagnosed glioblastoma, postoperative therapy involved the combined use of radiation and temozolomide. Bevacizumab treatment was also started at an early stage after surgery. RESULTS: In some patients, reduction of the residual tumor was observed at an early stage of chemoradiotherapy after the surgery, suggesting the positive effect of PDT. Recurrence occurred in 15 of the 18 patients during the course of treatment. Distant recurrence occurred in 8 of these 15 patients, despite good local tumor control. In the 14 patients with newly diagnosed glioblastoma, the median progression-free survival was almost 10.5 months, and the median overall survival was almost 16.9 months. CONCLUSIONS: PDT for malignant glioma is expected to slightly improve local tumor control for non-totally resectable lesions.


Assuntos
Neoplasias Encefálicas , Glioma , Fotoquimioterapia , Fármacos Fotossensibilizantes , Porfirinas , Humanos , Fotoquimioterapia/métodos , Masculino , Feminino , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Pessoa de Meia-Idade , Glioma/tratamento farmacológico , Idoso , Adulto , Neoplasias Encefálicas/tratamento farmacológico , Recidiva Local de Neoplasia , Temozolomida/uso terapêutico
12.
Int J Nanomedicine ; 19: 4701-4717, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38808148

RESUMO

Purpose: Numerous failures in melanoma treatment as a highly aggressive form of skin cancer with an unfavorable prognosis and excessive resistance to conventional therapies are prompting an urgent search for more effective therapeutic tools. Consequently, to increase the treatment efficiency and to reduce the side effects of traditional administration ways, herein, it has become crucial to combine photodynamic therapy as a promising therapeutic approach with the selectivity and biocompatibility of a novel colloidal transdermal nanoplatform for effective delivery of hybrid cargo with synergistic effects on melanoma cells. Methods: The self-assembled bilosomes, co-stabilized with L-α-phosphatidylcholine, sodium cholate, Pluronic® P123, and cholesterol, were designated, and the stability of colloidal vesicles was studied using dynamic and electrophoretic light scattering, also provided in cell culture medium (Dulbecco's Modified Eagle's Medium). The hybrid compounds - a classical photosensitizer (Methylene Blue) along with a complementary natural polyphenolic agent (curcumin), were successfully co-loaded, as confirmed by UV-Vis, ATR-FTIR, and fluorescent spectroscopies. The biocompatibility and usefulness of the polymer functionalized bilosome with loaded double cargo were demonstrated in vitro cyto- and phototoxicity experiments using normal keratinocytes and melanoma cancer cells. Results: The in vitro bioimaging and immunofluorescence study upon human skin epithelial (A375) and malignant (Me45) melanoma cell lines established the protective effect of the PEGylated bilosome surface. This effect was confirmed in cytotoxicity experiments, also determined on human cutaneous (HaCaT) keratinocytes. The flow cytometry experiments indicated the enhanced uptake of the encapsulated hybrid cargo compared to the non-loaded MB and CUR molecules, as well as a selectivity of the obtained nanocarriers upon tumor cell lines. The phyto-photodynamic action provided 24h-post irradiation revealed a more significant influence of the nanoplatform on Me45 cells in contrast to the A375 cell line, causing the cell viability rate below 20% of the control. Conclusion: As a result, we established an innovative and effective strategy for potential metastatic melanoma treatment through the synergism of phyto-photodynamic therapy and novel bilosomal-origin nanophotosensitizers.


Assuntos
Curcumina , Melanoma , Nanomedicina , Fotoquimioterapia , Fármacos Fotossensibilizantes , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/tratamento farmacológico , Melanoma/tratamento farmacológico , Fotoquimioterapia/métodos , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/administração & dosagem , Curcumina/química , Curcumina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Lipossomos/química , Lipossomos/farmacologia , Colesterol/química , Fosfatidilcolinas/química , Fosfatidilcolinas/farmacologia , Colato de Sódio/química , Sistemas de Liberação de Medicamentos/métodos , Poloxaleno/química , Poloxaleno/farmacologia
13.
Front Biosci (Landmark Ed) ; 29(5): 168, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38812303

RESUMO

The review focuses on the recent knowledge on natural anthraquinones (AQs) of plant origin and their potential for application in an exclusive medicinal curative and palliative method named photodynamic therapy (PDT). Green approach to PDT is associated with photosensitizers (PS) from plants or other natural sources and excitation light in visible spectrum. The investigations of plants are of high research interests due to their unique health supportive properties as herbs and the high percentage availability to obtain compounds with medical value. Up-to-date many naturally occurring compounds with therapeutic properties are known and are still under investigations. Some natural quinones have already been evaluated and clinically approved as anti-tumor agents. Recent scientific interests are beyond their common medical applications but also in directions to their photo-properties as natural PSs. The study presents a systematic searches on the latest knowledge on AQ derivatives that are isolated from the higher plants as photosensitizers for PDT applications. The natural quinones have been recognized with functions of natural dyes since the ancient times. Lately, AQs have been explored due to their biological activity including the photosensitive properties useful for PDT especially towards medical problems with no other alternatives. The existing literature' overview suggests that natural AQs possess characteristics of valuable PSs for PDT. This method is based on an application of a photoactive compound and light arrangement in oxygen media, such that the harmful general cytotoxicity could be avoided. Moreover, the common anticancer and antimicrobial drug resistance has been evaluated with very low occurrence after PDT. Natural AQs have been focused the scientific efforts to further developments because of the high range of natural sources, desirable biocompatibility, low toxicity, minimal side effects and low accident of drug resistance, together with their good photosensitivity and therapeutic capacity. Among the known AQs, only hypericin has been studied in anticancer clinical PDT. Currently, the natural PSs are under intensive research for the future PDT applications for diseases without alternative effective treatments.


Assuntos
Antraquinonas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Antraquinonas/farmacologia , Antraquinonas/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Humanos , Plantas/química
14.
Front Biosci (Landmark Ed) ; 29(5): 199, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38812322

RESUMO

BACKGROUND: Due to its non-invasive and widely applicable features, photodynamic therapy (PDT) has been a prominent treatment approach against cancer in recent years. However, its widespread application in clinical practice is limited by the dark toxicity of photosensitizers and insufficient penetration of light sources. This study assessed the anticancer effects of a novel photosensitizer 5-(4-amino-phenyl)-10,15,20-triphenylporphyrin with diethylene-triaminopentaacetic acid (ATPP-DTPA)-mediated PDT (hereinafter referred to as ATPP-PDT) under the irradiation of a 450-nm blue laser on colorectal cancer (CRC) in vivo and in vitro. METHODS: After 450-nm blue laser-mediated ATPP-PDT and the traditional photosensitizer 5-aminolevulinic acid (5-ALA)-PDT treatment, cell viability was detected through Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays. Reactive oxygen species (ROS) generation was quantified by flow cytometry and fluorescence microscopy. Western blotting and transcriptome RNA sequencing and functional experiments were used to evaluate cell apoptosis and its potential mechanism. Anti-tumor experiment in vivo was performed in nude mice with subcutaneous tumors. RESULTS: ATPP-DTPA had a marvelous absorption in the blue spectrum. Compared with 5-ALA, ATPP-DTPA could achieve significant killing effects at a lower dose. Owing to generating an excessive amount of ROS, 450-nm blue laser-mediated PDT based on ATPP-DTPA resulted in evident growth inhibition and apoptosis in CRC cells in vitro. After transcriptome RNA sequencing and functional experiments, p38 MAPK signaling pathway was confirmed to be involved in the regulation of apoptosis induced by 450-nm blue laser-mediated ATPP-PDT. Additionally, animal studies using xenograft model confirmed that ATPP-PDT had excellent anti-tumor effect and reasonable biosafety in vivo. CONCLUSIONS: PDT mediated by 450-nm blue laser combined with ATPP-DTPA may be a novel and effective method for the treatment of CRC.


Assuntos
Apoptose , Neoplasias Colorretais , Camundongos Nus , Fotoquimioterapia , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio , Fotoquimioterapia/métodos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/radioterapia , Apoptose/efeitos dos fármacos , Animais , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Humanos , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB C , Lasers , Sobrevivência Celular/efeitos dos fármacos , Ácido Aminolevulínico/farmacologia , Ácido Aminolevulínico/uso terapêutico
15.
Int J Nanomedicine ; 19: 4263-4278, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38766663

RESUMO

Introduction: Photodynamic Therapy (PDT) is a promising, minimally invasive treatment for cancer with high immunostimulatory potential, no reported drug resistance, and reduced side effects. Indocyanine Green (ICG) has been used as a photosensitizer (PS) for PDT, although its poor stability and low tumor-target specificity strongly limit its efficacy. To overcome these limitations, ICG can be formulated as a tumor-targeting nanoparticle (NP). Methods: We nanoformulated ICG into recombinant heavy-ferritin nanocages (HFn-ICG). HFn has a specific interaction with transferrin receptor 1 (TfR1), which is overexpressed in most tumors, thus increasing HFn tumor tropism. First, we tested the properties of HFn-ICG as a PS upon irradiation with a continuous-wave diode laser. Then, we evaluated PDT efficacy in two breast cancer (BC) cell lines with different TfR1 expression levels. Finally, we measured the levels of intracellular endogenous heavy ferritin (H-Fn) after PDT treatment. In fact, it is known that cells undergoing ROS-induced autophagy, as in PDT, tend to increase their ferritin levels as a defence mechanism. By measuring intracellular H-Fn, we verified whether this interplay between internalized HFn and endogenous H-Fn could be used to maximize HFn uptake and PDT efficacy. Results: We previously demonstrated that HFn-ICG stabilized ICG molecules and increased their delivery to the target site in vitro and in vivo for fluorescence guided surgery. Here, with the aim of using HFn-ICG for PDT, we showed that HFn-ICG improved treatment efficacy in BC cells, depending on their TfR1 expression. Our data revealed that endogenous H-Fn levels were increased after PDT treatment, suggesting that this defence reaction against oxidative stress could be used to enhance HFn-ICG uptake in cells, increasing treatment efficacy. Conclusion: The strong PDT efficacy and peculiar Trojan horse-like mechanism, that we revealed for the first time in literature, confirmed the promising application of HFn-ICG in PDT.


Assuntos
Neoplasias da Mama , Verde de Indocianina , Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Receptores da Transferrina , Verde de Indocianina/química , Verde de Indocianina/farmacocinética , Verde de Indocianina/farmacologia , Verde de Indocianina/administração & dosagem , Neoplasias da Mama/terapia , Neoplasias da Mama/tratamento farmacológico , Humanos , Feminino , Fotoquimioterapia/métodos , Linhagem Celular Tumoral , Receptores da Transferrina/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Nanopartículas/química , Apoferritinas/química , Ferritinas/química , Antígenos CD/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Células MCF-7
16.
Lasers Med Sci ; 39(1): 131, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38750381

RESUMO

Photodynamic therapy (PDT) is a targeted treatment method that utilizes a photosensitizer (PS) to induce cytotoxicity in malignant and non-malignant tumors. Optimization of PDT requires investigation of the selectivity of PS for the target tissues, irradiating light source, irradiation wavelengths, fluence rate, fluence, illumination mode, and overall treatment plan. In this study, we developed the Multi-mode Automatized Well-plate PDT LED Laboratory Irradiation System (MAWPLIS), an innovative device that automates time-consuming well plate light dosage/PS dose measurement experiment. The careful control of LED current and temperature stabilization in the LED module allowed the system to achieve high optical output stability. The MAWPLIS was designed by integrating a 3-axis moving system and motion controller, a quick-switching LED controller unit equipped with interchangeable LED modules capable of employing multiple wavelengths, and a TEC system. The proposed system achieved high optical output stability (1 mW) within the range of 0-500 mW, high wavelength stability (5 nm) at 635 nm, and high temperature stability (0.2 °C) across all radiation modes. The system's validation involved in vitro analysis using 5-ALA across varying concentrations, incubation periods, light exposures, and wavelengths in HT-29 colon cancer and WI-38 human lung fibroblast cell lines. Specifically, a combination of 405 nm and 635 nm wavelengths was selected to demonstrate enhanced strategies for colon cancer cell eradication and system validation. The MAWPLIS system represents a significant advancement in photodynamic therapy (PDT) research, offering automation and standardization of time-intensive experiments, high stability and precision, and improved PDT efficacy through dual-wavelength integration.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Fotoquimioterapia/métodos , Fotoquimioterapia/instrumentação , Humanos , Células HT29 , Ácido Aminolevulínico/administração & dosagem
17.
ACS Nano ; 18(20): 12933-12944, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38712906

RESUMO

Efficient tumor-targeted drug delivery is still a challenging and currently unbreakable bottleneck in chemotherapy for tumors. Nanomedicines based on passive or active targeting strategy have not yet achieved convincing chemotherapeutic benefits in the clinic due to the tumor heterogeneity. Inspired by the efficient inflammatory-cell recruitment to acute clots, we constructed a two-component nanosystem, which is composed of an RGD-modified pyropheophorbide-a (Ppa) micelle (PPRM) that mediates the tumor vascular-targeted photodynamic reaction to activate local coagulation and subsequently transmits the coagulation signals to the circulating clot-targeted CREKA peptide-modified camptothecin (CPT)-loaded nanodiscs (CCNDs) for amplifying tumor targeting. PPRM could effectively bind with the tumor vasculature and induce sufficient local thrombus by a photodynamic reaction. Local photodynamic reaction-induced tumor target amplification greatly increased the tumor accumulation of CCND by 4.2 times, thus significantly enhancing the chemotherapeutic efficacy in the 4T1 breast tumor model. In other words, this study provides a powerful platform to amplify tumor-specific drug delivery by taking advantage of the efficient crosstalk between the PPRM-activated coagulation cascade and clot-targeted CCND.


Assuntos
Clorofila , Nanopartículas , Fotoquimioterapia , Animais , Nanopartículas/química , Camundongos , Clorofila/análogos & derivados , Clorofila/química , Clorofila/farmacologia , Sistemas de Liberação de Medicamentos , Feminino , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Camptotecina/química , Camptotecina/farmacologia , Camptotecina/análogos & derivados , Camptotecina/administração & dosagem , Micelas , Camundongos Endogâmicos BALB C , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Oligopeptídeos/química , Oligopeptídeos/farmacologia
18.
Bioorg Chem ; 147: 107398, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38691907

RESUMO

Herein, we report a multifaceted nanoformulation, developed by binding thionine acetate (TA) in silica matrix to form TA loaded silica nanoparticles (STA Nps), which were characterized using various physicochemical techniques. STA NPs were spherical shaped having size 40-50 nm and exhibited good heating efficiency, improved photostability and singlet oxygen production rate than TA alone. In PDT experiment, the rate of degradation for ABDMA was enhanced from 0.1367 min-1 for TA alone to 0.1774 min-1 for STA Nps, depicting an increase in the reactive oxygen species (ROS) generation ability of STA Nps. Further, the cytotoxicity of STA Nps was investigated by carrying out the biophysical studies with Calf thymus DNA (Ct-DNA) and Human Serum Albumin (HSA). The results indicated that the binding of STA Nps to Ct-DNA causes alterations in the double helix structure of DNA and as a result, STA Nps can impart chemotherapeutic effects via targeting DNA. STA Nps showed good binding affinity with HSA without compromising the structure of HSA, which is important for STA Nps sustainable biodistribution and pharmacokinetics. Based on this study, it is suggested that because of the synergistic effect of chemo and phototherapy, STA Nps can be extensively utilized as potential candidates for treating cancer.


Assuntos
Antineoplásicos , Lasers , Nanopartículas , Fenotiazinas , Dióxido de Silício , Humanos , Dióxido de Silício/química , Nanopartículas/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Fenotiazinas/química , Fenotiazinas/farmacologia , Fenotiazinas/síntese química , Albumina Sérica Humana/química , DNA/química , Ensaios de Seleção de Medicamentos Antitumorais , Relação Dose-Resposta a Droga , Estrutura Molecular , Animais , Espécies Reativas de Oxigênio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Fotoquimioterapia , Proliferação de Células/efeitos dos fármacos , Bovinos , Relação Estrutura-Atividade
19.
J Appl Oral Sci ; 32: e20230447, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38695448

RESUMO

OBJECTIVE: To evaluate whether antimicrobial photodynamic therapy (aPDT) repairs bisphosphonate-related osteonecrosis of the jaw (BRONJ) modulated by the reduction of NF-kB protein in a murine model. METHODOLOGY: Male Wistar rats (N=30) were divided into the following groups (n=6/group): negative control (NC); experimental osteonecrosis (ONE); ONE + photosensitizer (PS); ONE + photobiomodulation (PBM); and ONE + aPDT. Over 8 weeks, ONE was induced by zoledronic acid 250 µg/kg injections, except in the NC group, which received sterile 0.9% saline, followed by extraction of the lower left first molar. Red light laser irradiation (wavelength ~660 nm, power 50 mW, energy of 2 J, energy dose of 66.67 J/cm2 for 40 s) was performed once a week for 4 weeks. Methylene blue 0.3% was used as PS. The animals were euthanized and examined macroscopically for the presence of exposed bone and epithelial repair and microscopically by histochemical (hematoxylin-eosin and Masson's trichrome staining) and immunohistochemical (anti-NF-kB) methods. Macroscopic and histomorphometric data were analyzed by one-way ANOVA and Tukey's post-test (p<0.05). RESULTS: Mucosal repair, viable osteocytes, and NF-kB immunostaining were observed in the NC, ONE+PS, ONE+PBM, and ONE+aPDT groups. The ONE group showed no mucosal repair, showing empty lacunae and multifocal immunostaining for NF-kB. The ONE+PBM and ONE+aPDT groups had greater deposition of extracellular matrix and less necrotic bone tissue (p<0.05). CONCLUSION: PBM and aPDT treatments for BRONJ were effective for bone and epithelial repair, in addition to reducing inflammation mediated by the decrease of NF-kB protein in the irradiated regions.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Modelos Animais de Doenças , Imuno-Histoquímica , NF-kappa B , Fotoquimioterapia , Fármacos Fotossensibilizantes , Ratos Wistar , Animais , Masculino , Fotoquimioterapia/métodos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , NF-kappa B/análise , Fármacos Fotossensibilizantes/farmacologia , Fatores de Tempo , Reprodutibilidade dos Testes , Ácido Zoledrônico/farmacologia , Resultado do Tratamento , Imidazóis/farmacologia , Difosfonatos/farmacologia , Terapia com Luz de Baixa Intensidade/métodos , Azul de Metileno/farmacologia , Azul de Metileno/uso terapêutico , Análise de Variância , Distribuição Aleatória , Conservadores da Densidade Óssea/farmacologia
20.
Anal Chim Acta ; 1311: 342734, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38816163

RESUMO

Photodynamic therapy (PDT), characterized by high treatment efficiency, absence of drug resistance, minimal trauma, and few side effects, has gradually emerged as a novel and alternative clinical approach compared to traditional surgical resection, chemotherapy and radiation. Whereas, considering the limited diffusion distance and short lifespan of reactive oxygen species (ROS), as well as the hypoxic tumor microenvironment, it is crucial to design photosensitizers (PSs) with suborganelle specific targeting ability and low-oxygen dependence for accurate and highly efficient photodynamic therapy. In this study, we have meticulously designed three PSs, namely CIH, CIBr, and CIPh, based on molecular engineering. Theoretical calculation demonstrate that the three compounds possess good molecular planarity with calculated S1-T1 energy gaps (ΔES1-T1) of 1.04 eV for CIH, 0.92 eV for CIBr, and 0.84 eV for CIPh respectively. Notably, CIPh showcases remarkable dual subcellular targeting capability towards lipid droplets (LDs) and mitochondria owing to the synergistic effect of lipophilicity derived from coumarin's inherent properties combined with electropositivity conferred by indole salt cations. Furthermore, CIPh demonstrates exclusive release of singlet oxygen (1O2)and highly efficient superoxide anion free radicals(O2⦁-) upon light irradiation supported by its smallest S1-T1 energy gap (ΔES1-T1 = 0.84 eV). This leads to compromised integrity of LDs along with mitochondrial membrane potential, resulting in profound apoptosis induction in HepG2 cells. This successful example of molecular engineering guided by density functional theory (DFT) provides valuable experience for the development of more effective PSs with superior dual targeting specificity. It also provides a new idea for the development of advanced PSs with efficient and accurate ROS generation ability towards fluorescence imaging-guided hypoxic tumor therapy.


Assuntos
Gotículas Lipídicas , Mitocôndrias , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio , Humanos , Espécies Reativas de Oxigênio/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Gotículas Lipídicas/química , Gotículas Lipídicas/metabolismo , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fotoquimioterapia , Sobrevivência Celular/efeitos dos fármacos
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