RESUMO

Photodynamic therapy (PDT) uses a photosensitizer to generate reactive oxygen species (ROS) that kill target cells. In cancer treatments, PDT can potentially induce immunogenic cell death (ICD), which is characterized by a well-controlled exposure of damage-associated molecular patterns (DAMPs) that activate dendritic cells (DCs) and consequently modulate the immune response in the tumor microenvironment. However, PDT still has limitations, such as the activity of photosensitizers in aqueous media and poor bioavailability. Therefore, a new photosensitizer system, SLN-AlPc, has been developed to improve the therapeutic efficacy of PDT. In vitro experiments showed that the light-excited nanocarrier increased ROS production in murine melanoma B16-F10 cells and modulated the profile of DCs. PDT induced cell death accompanied by the exposure of DAMPs and the formation of autophagosomes. In addition, the DCs exposed to PDT-treated B16-F10 cells exhibited morphological changes, increased expression of MHCII, CD86, CD80, and production of IL-12 and IFN-γ, suggesting immune activation towards an antitumor profile. These results indicate that the SLNs-AlPc protocol has the potential to improve PDT efficacy by inducing ICD and activating DCs.

RESUMO

Glioblastoma (GBM) is an aggressive brain cancer characterized by significant molecular and cellular heterogeneity, which complicates treatment efforts. Current standard therapies, including surgical resection, radiation, and temozolomide (TMZ) chemotherapy, often fail to achieve long-term remission due to tumor recurrence and resistance. A pro-oxidant environment is involved in glioma progression, with oxidative stress contributing to the genetic instability that leads to gliomagenesis. Evaluating pro-oxidant therapies in brain tumors is crucial due to their potential to selectively target and eradicate cancer cells by exploiting the elevated oxidative stress levels inherent in these malignant cells, thereby offering a novel and effective strategy for overcoming resistance to conventional therapies. This study investigates the therapeutic potential of doxorubicin (DOX) and photodynamic therapy (PDT) with Me-ALA, focusing on their effects on redox homeostasis. Basal ROS levels and antioxidant gene expression (NFE2L2, CAT, GSR) were quantitatively assessed across GBM cell lines, revealing significant variability probably linked to genetic differences. DOX and PDT treatments, both individually and in combination, were analyzed for their efficacy in inducing oxidative stress and cytotoxicity. An in silico analysis further explored the relationship between gene mutations and oxidative stress in GBM patients, providing insights into the molecular mechanisms underlying treatment responses. Our findings suggest that pro-oxidant therapies, such as DOX and PDT in combination, could selectively target GBM cells, highlighting a promising avenue for improving therapeutic outcomes in GBM.

Assuntos

Neoplasias Encefálicas , Doxorrubicina , Glioblastoma , Estresse Oxidativo , Fotoquimioterapia , Espécies Reativas de Oxigênio , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioblastoma/genética , Humanos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Fotoquimioterapia/métodos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Sinergismo Farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico

RESUMO

Bioluminescence resonance energy transfer photodynamic therapy, which uses light generated by bioluminescent proteins to activate photosensitizers and produce reactive oxygen species without the need for external irradiation, has shown promising results in cancer models. However, the characterization of delivery systems that can incorporate the components of this therapy for preferential delivery to the tumor remains necessary. In this work, we have characterized parvovirus B19-like particles (B19V-VLPs) as a platform for a photosensitizer and a bioluminescent protein. By chemical and biorthogonal conjugation, we conjugated rose Bengal photosensitizer and firefly luciferase to B19V-VLPs and a protein for added specificity. The results showed that B19V-VLPs can withstand decoration with all three components without affecting its structure or stability. The conjugated luciferase showed activity and was able to activate rose Bengal to produce singlet oxygen without the need for external light. The photodynamic reaction generated by the functionalized VLPs-B19 can decrease the viability of tumor cells in vitro and affect tumor growth and metastasis in the 4 T1 model. Treatment with functionalized VLPs-B19 also increased the percentage of CD4 and CD8 cell populations in the spleen and in inguinal lymph nodes compared to vehicle-treated mice. Our results support B19V-VLPs as a delivery platform for bioluminescent photodynamic therapy components to solid tumors.

Assuntos

Fotoquimioterapia , Fármacos Fotossensibilizantes , Rosa Bengala , Animais , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Camundongos , Rosa Bengala/química , Rosa Bengala/farmacologia , Rosa Bengala/uso terapêutico , Linhagem Celular Tumoral , Humanos , Oxigênio Singlete/metabolismo , Parvovirus B19 Humano/efeitos dos fármacos , Parvovirus B19 Humano/química , Neoplasias/tratamento farmacológico , Luciferases de Vaga-Lume/metabolismo , Feminino

RESUMO

The purpose of this study was to evaluate the current scientific evidence on the effectiveness of antimicrobial photodynamic therapy (aPDT) as an adjunctive treatment to mechanical debridement in the treatment of peri-implantitis. The Preferred Reporting Items for Systematic Reviews and Meta-analyses was followed. A protocol was registered in the International Prospective Registry of Systematic Reviews (PROSPERO #CRD42022361684). The search was carried out in seven databases, with no restrictions regarding language or year of publication. Our work included studies that compared clinical periodontal parameters between individuals treated with mechanical debridement associated with aPDT and a control group of patients who had undergone mechanical debridement alone. Study selection, data extraction, and risk of bias assessment (RoB 2.0) were performed by two review authors. Meta-analysis was performed. The mean difference (MD) and a 95% confidence interval (CI) were provided. Four hundred and seven-four studies were identified, of which five studies were included. The meta-analysis demonstrated that aPDT adjunctive to mechanical debridement in subjects with peri-implantitis resulted in greater reduction in probing depth 3 months after treatment than among subjects receiving treatment with mechanical debridement. Most of the included studies exhibit a low risk of bias. Adjunctive aPDT to mechanical debridement contributes to the improvement of peri-implant clinical parameters in individuals with peri-implantitis, in particular probing depth.

Assuntos

Peri-Implantite , Fotoquimioterapia , Humanos , Peri-Implantite/tratamento farmacológico , Peri-Implantite/terapia , Fotoquimioterapia/métodos , Resultado do Tratamento , Anti-Infecciosos/uso terapêutico , Desbridamento/métodos

RESUMO

Oral squamous cell carcinoma (OSCC) constitutes over 90% of oral cancers, known for its aggressiveness and poor prognosis. Photodynamic therapy (PDT) has emerged as a promising adjuvant therapy and is linked to immunogenic cell death, activating innate and adaptive anti-tumor responses. Natural Killer (NK) cells, key players in malignant cell elimination, have not been extensively studied in PDT. This study evaluates whether PDT increases OSCC cell lines' susceptibility to NK cell cytotoxicity. PDT, using 5-aminolevulinic acid (5-ALA) and LED irradiation, was applied to Ca1 and Luc4 cell lines. Results showed a dose-dependent viability decrease post-PDT. Gene expression analysis revealed upregulation of NK cell-activating ligands (ULBP1-4, MICA/B) and decreased MHC class I expression in Ca1, suggesting increased NK cell susceptibility. Enhanced NK cell cytotoxicity was confirmed in Ca1 but not in Luc4 cells. These findings indicate that PDT may enhance NK cell-mediated cytotoxicity in OSCC, offering potential for improved treatment strategies.

RESUMO

Curcumin serves as a photosensitizer (PS) in the context of microbial inactivation when subjected to light exposure, to produce reactive oxygen species, which exhibit efficacy in eradicating microorganisms. This remarkable property underscores the growing potential of antimicrobial photodynamic therapy (aPDT) in the ongoing fight against bacterial infections. Considering this, we investigate the efficacy of various in vitro curcumin formulations within a PDT protocol designed to target Staphylococcus aureus. Specifically, we conduct a comparative analysis involving synthetic curcumin (Cur-Syn) and curcumin derivatives modified with chlorine (Cl), selenium (Se), and iodine (I) (Cur-Cl, Cur-Se, Cur-I). To assess the impact of aPDT, we subject S. aureus to incubation with curcumin, followed by irradiation at 450 nm with energy doses of 3.75, 7.5, and 15 J/cm2. Our investigation encompasses an evaluation of PS uptake and photobleaching across the various curcumin variants. Notably, all three modifications (Cur-Cl, Cur-Se, Cur-I) induce a significant reduction in bacterial viability, approximately achieving a 3-log reduction. Interestingly, the uptake kinetics of Cur-Syn and Cur-Se exhibit similarities, reaching saturation after 20 min. Our findings suggest that modifications to curcumin have a discernible impact on the photodynamic properties of the PS molecule.

RESUMO

Melanogenesis-stimulated B16-F10 cells enter in a quiescent state, present inhibited mitochondrial respiration and increased reactive oxygen species levels. These alterations suggest that these cells may be under redox signaling, allowing tumor survival. The aim of this study was to evaluate redox-modified proteins in B16-F10 cells after melanogenesis stimulation and rose bengal-photodynamic therapy (RB-PDT). A redox proteomics label-free approach based on the biotin switch assay technique with biotin-HPDP and N-ethylmaleimide was used to assess the thiol-oxidized protein profile. Aconitase was oxidized at Cys-448 and Cys-451, citrate synthase was oxidized at Cys-202 and aspartate aminotransferase (Got2) was oxidized at Cys-272 and Cys-274, exclusively after melanogenesis stimulation. After RB-PDT, only guanine nucleotide-binding protein subunit beta-2-like 1 (Gnb2l1) was oxidized (Cys-168). In contrast, melanogenesis stimulation followed by RB-PDT led to the oxidation of different cysteines in Gnb2l1 (Cys-153 and Cys-249). Besides that, glyceraldehyde-3-phosphate dehydrogenase (Gapdh) presented oxidation at Cys-245, peptidyl-prolyl cis-trans isomerase A (Ppia) was oxidized at Cys-161 and 5,6-dihydroxyindole-2-carboxylic acid oxidase (Tyrp1) was oxidized at Cys-65, Cys-30, and Cys-336 after melanogenesis stimulation followed by RB-PDT. The redox alterations observed in murine melanoma cells and identification of possible target proteins are of great importance to further understand tumor resistance mechanisms.

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

RESUMO

Photodynamic therapy (PDT) has developed as an efficient strategy for cancer treatment. PDT involves the production of reactive oxygen species (ROS) by light irradiation after activating a photosensitizer (PS) in the presence of O2. PS-coupled nanomaterials offer additional advantages, as they can merge the effects of PDT with conventional enabling-combined photo-chemotherapeutics effects. In this work, mesoporous titania nanorods were surface-immobilized with Chlorin e6 (Ce6) conjugated through 3-(aminopropyl)-trimethoxysilane as a coupling agent. The mesoporous nanorods act as nano vehicles for doxorubicin delivery, and the Ce6 provides a visible light-responsive production of ROS to induce PDT. The nanomaterials were characterized by XRD, DRS, FTIR, TGA, N2 adsorption-desorption isotherms at 77 K, and TEM. The obtained materials were tested for their singlet oxygen and hydroxyl radical generation capacity using fluorescence assays. In vitro cell viability experiments with HeLa cells showed that the prepared materials are not cytotoxic in the dark, and that they exhibit photodynamic activity when irradiated with LED light (150 W m-2). Drug-loading experiments with doxorubicin (DOX) as a model chemotherapeutic drug showed that the nanostructures efficiently encapsulated DOX. The DOX-nanomaterial formulations show chemo-cytotoxic effects on Hela cells. Combined photo-chemotoxicity experiments show enhanced effects on HeLa cell viability, indicating that the conjugated nanorods are promising for use in combined therapy driven by LED light irradiation.

RESUMO

BACKGROUND: To compare photodynamic therapy and the use of probiotics in reducing halitosis assessed through gas chromatography and microbiome analysis. METHODS: Participants aged from 18 to 25 years showing sulfide (SH2) ≥ 112 ppb on gas chromatography were selected. They were divided into four treatment groups: Group 1-Tongue Scraping; Group 2-Antimicrobial Photodynamic Therapy (aPDT); Group 3-Probiotics; and Group 4-Antimicrobial Photodynamic Therapy (aPDT) and Probiotics. The halimetry process was performed before, immediately after the treatments, and 7 days, 14 days, and 30 days after the initial collection. The collections for later microbiological analysis were made along with the halimetry for microbiome analysis. RESULTS: Treatment with aPDT or probiotics under these experimental conditions was not able to change the bacteria present in the biofilm of the tongue. CONCLUSIONS: More research is needed to know the behavior of the oral microbiome in the presence of halitosis and the effectiveness of new treatments.