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1.
Pharmaceuticals (Basel) ; 17(6)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38931400

RESUMO

This study assessed the effectiveness of a trastuzumab-targeted 177Lu-labeled mesoporous Carbon@Silica nanostructure (DOTA@TRA/MC@Si) for HER2-positive breast cancer treatment, focusing on its uptake, internalization, and efflux in breast cancer cells. The synthesized PEI-MC@Si nanocomposite was reacted with DOTA-NHS-ester, confirmed by the Arsenazo(III) assay. Following this, TRA was conjugated to the DOTA@PEI-MC@Si for targeting. DOTA@PEI-MC@Si and DOTA@TRA/MC@Si nanocomposites were labeled with 177Lu, and their efficacy was evaluated through in vitro radiolabeling experiments. According to the results, the DOTA@TRA/MC@Si nanocomposite was successfully labeled with 177Lu, yielding a radiochemical yield of 93.0 ± 2.4%. In vitro studies revealed a higher uptake of the [177Lu]Lu-DOTA@TRA/MC@Si nanocomposite in HER2-positive SK-BR-3 cells (44.0 ± 4.6% after 24 h) compared to MDA-MB-231 cells (21.0 ± 2.3%). The IC50 values for TRA-dependent uptake in the SK-BR-3 and BT-474 cells were 0.9 µM and 1.3 µM, respectively, indicating affinity toward HER-2 receptor-expressing cells. The lipophilic distribution coefficients of the radiolabeled nanocomposites were determined to be 1.7 ± 0.3 for [177Lu]Lu-DOTA@TRA/MC@Si and 1.5 ± 0.2 for [177Lu]Lu-DOTA@PEI-MC@Si, suggesting sufficient passive transport through the cell membrane and increased accumulation in target tissues. The [177Lu]Lu-DOTA@TRA/MC@Si nanocomposite showed an uptake into HER2-positive cell lines, marking a valuable step toward the development of a nanoparticle-based therapeutic agent for an improved treatment strategy for HER2-positive breast cancer.

2.
ACS Omega ; 8(29): 26287-26300, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37521641

RESUMO

Triple-negative breast cancer (TNBC) tends to behave more aggressively compared to other breast cancer subtypes due to the lack of receptors and its limited targeting therapy. In recent years, nanotechnology advancement has led to the development of various nanoparticle platforms for the targeted treatment of cancers. Especially, HSA-NPs have specific advantages such as biocompatibility, adjustable size during production, and relatively easy synthesis. In this study, HSA-NPs were encapsulated with docetaxel (DTX) and functionalized with polyethylene glycol (PEG), also becoming a targeting nanoplatform modified with durvalumab (DVL), and the whole nanostructure was well characterized. Subsequently, drug release studies and various in vitro cell culture studies such as determining the cytotoxicity and apoptotic levels of the nanoplatforms and PD-L1 using ELISA test were conducted on MDA-MB-468, MDA-MB-231, and MCF-7 cells. According to the results, HSA-DTX@PEG-DVL NPs showed better cytotoxicity compared to DTX in all the three cell lines. In addition, it was observed that the HSA-DTX@PEG-DVL NPs did not lead the cells to late apoptosis but were effective in the early apoptotic stage. Moreover, the ELISA data showed a significantly induced PD-L1 expression due to the presence of DVL in the nanostructure, which indicates that DVL antibodies successfully bind to the HSA-DTX@PEG-DVL nanostructure.

3.
Appl Biochem Biotechnol ; 195(3): 1904-1927, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36401724

RESUMO

In cancer treatment, the complexity of tumors seriously affects the therapeutic potential of the treatment. Treatments with combination therapy result in more potent effects than monotherapy or their theoretical combination in cancer treatment. Photothermal therapy (PTT) includes applying phototherapeutic agents that cause local hyperthermia responsible for the thermal ablation of tumor cells after applying near-infrared light and is often applied with other combination therapies. In this study, the chemo-PTT potential of synthesized drug-loaded and targeted GEM/TRA-MC@Si nanocomposite on Her2 positive breast cancer cell line (SK-BR-3) and human triple-negative breast cancer cell line (MDA-MB-231) was investigated using NIR application as in vitro. First, the cell viability (IC50) value of the GEM/TRA-MC@Si nanocomposite was determined as 25 µg/µL. Then, chemo-PTT was performed, and the viability of the cells was evaluated. In addition, the live/dead cell rate was established by staining with the Calcein-AM and EthD-1, and apoptosis tests were completed. When the surface temperature of Her2 positive SK-BR-3 cells exceeded 47 °C during PTT with an irradiation time of > 100 s, it caused cell death. In this study, it was demonstrated that in vitro PTT (1 W/cm2, 180 s) was applied using GEM/TRA-MC@Si nanocomposite (25 µg/mL) on her2 + SK-BR-3 cell line, which contributed to the reduction of cell viability. In addition, this study demonstrates that chemo-PTT with targeted GEM/TRA-MC@Si nanocomposite induced SK-BR-3 cell viability and can initiate cell death through the apoptosis pathway under optimized irradiation conditions. Herewith chemo-PTT combination therapy of targeted GEM-TRA/MC@Si nanocomposite was found to be effective on SK-BR-3 cells as in vitro.


Assuntos
Nanocompostos , Nanopartículas , Neoplasias , Humanos , Terapia Fototérmica , Carbono , Dióxido de Silício , Terapia Combinada , Linhagem Celular Tumoral , Doxorrubicina/farmacologia
4.
Biomed Mater ; 17(6)2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36137521

RESUMO

The antimicrobial properties of scaffolds designed for use in wound healing are accepted as an important factor in the healing process to accelerate the wound healing process without causing inflammation. For this purpose, chitosan-polyvinyl alcohol composite membranes loaded with Cu2ZnSnSe4quantum dots (CZTSe QDs) as an antibacterial and cytocompatible biomaterial to regulate the wound healing process were produced. CZTSe QDs particles were synthesized under hydrothermal conditions. Polymer-based nanocomposites with different concentrations of the synthesized nanoparticles were produced by the solvent casting method. After detailed physicochemical and morphological characterizations of CZTSe QDs and composite membranes, antibacterial activities and cell viability were extensively investigated against gram-positive and gram-negative bacterial and yeast strains, and L929 mouse fibroblast cells lines, respectively. The results show that the preparation of composite scaffolds at a QDs concentration of 3.3% by weight has the best antimicrobial activity. Composite scaffold membranes, which can be obtained as a result of an easy production process, are thought to have great potential applications in tissue engineering as wound dressing material due to their high mechanical properties, wettability, strong antibacterial properties and non-toxicity.


Assuntos
Anti-Infecciosos , Quitosana , Nanocompostos , Pontos Quânticos , Animais , Antibacterianos/química , Bandagens , Materiais Biocompatíveis/química , Quitosana/química , Camundongos , Nanocompostos/química , Polímeros , Álcool de Polivinil/química , Solventes
5.
Photodiagnosis Photodyn Ther ; 36: 102518, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34478898

RESUMO

This study aims to investigate the photodynamic therapy (PDT) effects on MeWo (human melanoma cells) and HaCaT (normal human keratinocyte cells) by light stimulation of different concentrations of Zinc (II)-tetra-tert-butyl-phthalocyaninato (ZnPc). MTT viability assay data indicated that a 25 µM concentration of ZnPc is cytotoxic to the melanoma cancer cells while this concentration of ZnPc is not cytotoxic for the HaCaT cell line. Moreover, the results showed that photoactivated ZnPc at 12.5 µM concentration reduced the cell viability of the MeWo cell line to about 50 %. At this photosensitizing concentration, the efficacy of light doses of 20, 30, 40, and 50 J/cm2 was evaluated against MeWo and HaCaT cells. ZnPc at a concentration of 12.5 µM activated with a light dose of 50 J/cm2 was the most efficient for the killing of MeWo cells. In conclusion, the 12.5 µM of ZnPc with the treatment light dose of 50 J/cm2 from a RED light source was adequate to destroy MeWo cells by the ROS-induced apoptosis mechanism. It also exhibited low killing effects on healthy HaCaT cells. These findings are supported by the results of apoptosis with the Annexin V & Dead Cell Kit and fluorescence imaging.


Assuntos
Melanoma , Compostos Organometálicos , Fotoquimioterapia , Apoptose , Linhagem Celular Tumoral , Humanos , Isoindóis , Melanoma/tratamento farmacológico , Compostos Organometálicos/farmacologia , Compostos Organometálicos/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Zinco/farmacologia
6.
Eur J Breast Health ; 17(3): 214-219, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34263148

RESUMO

Radiopharmaceutical therapy (RPT) is an effective and safe treatment for many types of cancer. RPT acts by binding radioactive atoms to tumor-associated antigens, monoclonal antibodies, nanoparticles, peptides, and small molecules. These treatments ensure that a concentrated dose is delivered to the targeted tumor tissue while preserving the normal tissues surrounding the tumor. Given these features, RPT is superior to traditional methods. This review article aimed to performa comprehensive review and evaluation of the potential of radionuclides and radiopharmaceuticals used in breast cancer treatment in preclinical studies conducted in the last five years.

7.
Front Cell Infect Microbiol ; 11: 678081, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178721

RESUMO

Introduction: The use of spinal implants for the treatment of back disorders is largely affected by the insurgence of infections at the implantation site. Antibacterial coatings have been proposed as a viable solution to limit such infections. However, despite being effective at short-term, conventional coatings lack the ability to prevent infections at medium and long-term. Hydrogel-based drug delivery systems may represent a solution controlling the release of the loaded antibacterial agents while improving cell integration. Agarose, in particular, is a biocompatible natural polysaccharide known to improve cell growth and already used in drug delivery system formulations. In this study, an agarose hydrogel-based coating has been developed for the controlled release of gentamicin (GS). Methods: Sand blasted Ti6Al4V discs were grafted with dopamine (DOPA) solution. After, GS loaded agarose hydrogels have been produced and additioned with tannic acid (TA) and calcium chloride (CaCl2) as crosslinkers. The different GS-loaded hydrogel formulations were deposited on Ti6Al4V-DOPA surfaces, and allowed to react under UV irradiation. Surface topography, wettability and composition have been analyzed with profilometry, static contact angle measurement, XPS and FTIR spectroscopy analyses. GS release was performed under pseudo-physiological conditions up to 28 days and the released GS was quantified using a specific ELISA test. The cytotoxicity of the produced coatings against human cells have been tested, along with their antibacterial activity against S. aureus bacteria. Results: A homogeneous coating was obtained with all the hydrogel formulations. Moreover, the coatings presented a hydrophilic behavior and micro-scale surface roughness. The addition of TA in the hydrogel formulations showed an increase in the release time compared to the normal GS-agarose hydrogels. Moreover, the GS released from these gels was able to significantly inhibit S. aureus growth compared to the GS-agarose hydrogels. The addition of CaCl2 to the gel formulation was able to significantly decrease cytotoxicity of the TA-modified hydrogels. Conclusions: Due to their surface properties, low cytotoxicity and high antibacterial effects, the hereby proposed gentamicin-loaded agarose-hydrogels provide new insight, and represent a promising approach for the surface modification of spinal implants, greatly impacting their application in the orthopedic surgical scenario.


Assuntos
Gentamicinas , Titânio , Antibacterianos/farmacologia , Materiais Revestidos Biocompatíveis , Preparações de Ação Retardada , Dopamina , Gentamicinas/farmacologia , Humanos , Hidrogéis , Sefarose , Staphylococcus aureus
8.
Biopharm Drug Dispos ; 42(6): 285-293, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33904176

RESUMO

Early detection of the site of infection non-invasively with radiolabeled molecules is important for the success of treatment. Technetium-99m labeled antibiotics have the potential to discriminate between bacterial infection and sterile inflammation. Sultamicillin is the tosylate salt of the double ester of sulbactam plus ampicillin. In this study, sultamicillin was labeled with 99m Tc according to the stannous chloride method. Quality control studies of radiolabeled sultamicillin were performed by radiochromatographic methods. In vitro binding assays were performed in live and heat-killed gram-positive Staphylococcus aureus and gram-negative Escherichia coli strains. The radiolabeling yield of 99m Tc-sultamicillin was determined as 97.8% ± 3.1% (n = 5). The maximum bacterial uptake of 99m Tc-sultamicillin was 80.7% ± 11.00% at 4 h for living S. aureus and 93.2% ± 4.40% at 2 h for E. coli. Bacterial uptake study results show that sultamicillin has the potential to be a nuclear imaging agent, especially in infections caused by gram-negative E. coli and gram-positive S. aureus.


Assuntos
Antibacterianos/administração & dosagem , Escherichia coli/metabolismo , Staphylococcus aureus/metabolismo , Tecnécio , Ampicilina/administração & dosagem , Infecções por Escherichia coli/diagnóstico por imagem , Infecções Estafilocócicas/diagnóstico por imagem , Sulbactam/administração & dosagem , Compostos de Estanho
9.
Curr Med Imaging ; 17(6): 781-789, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33372880

RESUMO

BACKGROUND: Infective endocarditis (IE) is an infection of the heart's endocardial surface. In recent years, nuclear imaging methods have gained importance in the diagnosis of IE. The present study aims to investigate the imaging potential of 99mTc-labeled vancomycin (99mTc-Vancomycin) as a new agent that would enable the diagnosis of IE in its early stages when it is difficult to diagnose or has small vegetation in the experimental rat model. METHODS: 99mTc-Vancomycin scintigraphy was evaluated for its accumulation in IE with Staphylococcus aureus performed in an experimental rat model. Serial planar scintigraphic and biodistribution analysis of infected vegetations are compared to rats with sterile vegetations. The heart was identified as an infected organ, the liver was identified as a non-infected organ and the heart/liver uptake ratio (T / NT ratio) was compared between infective endocarditis and sterile endocarditis groups. RESULTS: Planar scintigrams (in vivo measurements) showed more uptake in the heart of rats in the infective endocarditis group compared to the uptake in the heart of rats in the sterile endocarditis group, but this difference was not statistically significant (p>0.05). From the ex vivo measurements, the 99mTc-Vancomycin heart uptake increased significantly (p = 0.016), liver uptake was significantly decreased (p = 0.045) and the T/NT ratio was significantly higher (p = 0.014) in the infective endocarditis group compared to the sterile endocarditis group. CONCLUSION: In this experimental study, 99mTc-Vancomycin scintigraphy ensured the detection of ex vivo infected tissue in a rat model of IE. In addition, the absence of significant 99mTc-Vancomycin uptake in the sterile endocarditis group indicates that this agent targeted the infected tissue instead of the sterile inflammatory tissue. Finally, this agent should also be evaluated with animal- specific imaging devices.


Assuntos
Endocardite , Tecnécio , Animais , Endocardite/diagnóstico por imagem , Ratos , Distribuição Tecidual , Tomografia Computadorizada por Raios X , Vancomicina
10.
Mol Pharm ; 17(7): 2648-2659, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32412765

RESUMO

Photodynamic therapy (PDT) is a noninvasive therapy based on the photodynamic effect. In this study, we sought to determine intracellular uptake and in vivo photodynamic therapy potential of Zn phthalocyanine-loaded mesoporous silica nanoparticles (MSNP5) against pancreatic cancer cells. MSNP5 were labeled with 131I; the radiolabeling efficiency was found to 95.5 ± 1.2% in pH 9 and 60 min reaction time. Besides, the highest intracellular uptake yields of 131I-MSNP5 nanoparticles in MIA PaCa-2, AsPC-1, and PANC-1 cells were determined as 43.9 ± 3.8%, 41.8 ± 0.2%, and 37.9 ± 1.3%, respectively, at 24 h incubation time. In vivo PDT studies were performed with subcutaneous xenograft cancer model nude mice with AsPC-1 pancreatic cancer cells. For photodynamic therapy, 685 nm red laser light 100 J/cm2 light dose using and 5-20 µM ZnPc containing MSNP5 concentrations were applied. Histopathological studies revealed that the ratio of necrosis in tumor tissue was higher in the treatment group than the control groups.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Cetuximab/administração & dosagem , Indóis/administração & dosagem , Nanopartículas Metálicas/química , Compostos Organometálicos/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Animais , Linhagem Celular Tumoral , Terapia Combinada/métodos , Humanos , Concentração de Íons de Hidrogênio , Indóis/química , Radioisótopos do Iodo/química , Isoindóis , Lasers , Luz , Masculino , Camundongos , Camundongos Nus , Nanopartículas , Necrose , Compostos Organometálicos/química , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/radioterapia , Dióxido de Silício/química , Ensaios Antitumorais Modelo de Xenoenxerto , Compostos de Zinco
11.
Photodiagnosis Photodyn Ther ; 30: 101715, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32165338

RESUMO

Antimicrobial resistance is one of the most important causes of morbidity and mortality in the treatment of infectious diseases worldwide. Candida albicans is one of the most virulent and common species of fungi to cause invasive fungal infections on humans. Alternative treatment strategies, including photodynamic therapy, are needed for controlling these infectious diseases. The aim of this study was to investigate the antifungal photodynamic activities of phthalocyanine derivatives on C. albicans. The minimum inhibitory concentration (MIC) values of compounds were determined by the broth microdilution method. Uptake of the compounds in C. albicans and dark toxicity of the compounds were also investigated. Photodynamic inhibition of growth experiments was performed by measuring the colony-forming unit/mL (CFU/mL) of the strain. Maximum uptake into the cells was observed in the presence of 64 µg/mL concentration for each compound except for ZnPc. Compounds did not show dark toxicity/inhibitory effects at sub-MIC concentrations on C. albicans when compared to the negative control groups. Zn(II)Pc, ZnPc, and ZnPc-TiO2 showed fungicidal effect after irradiation with the light dose of 90 J/cm2 in the presence of the compounds. In addition to the fungicidal effects, SubPc, SubPc-TiO2, Es-SiPc, and Es-SubPc compounds were also found to have inhibitory effects on the growth of yeast cells after irradiation.


Assuntos
Candida albicans , Fotoquimioterapia , Antifúngicos/farmacologia , Humanos , Indóis , Isoindóis , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia
12.
Heliyon ; 5(10): e02607, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31667420

RESUMO

A series of imidazolium bromide salts (NIM-Br 1a, 1b and 1c) bearing different lengths of alkyl chains were synthesized and theirin vitro antibacterial activities were determined by measuring the minimum inhibitory concentration (MIC) values for Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Enterococcus faecalis. In addition, these imidazolium derivatives were also evaluated against biofilm produced by these bacterial strains. All compounds were found to be effective against Gram-positive and Gram-negative bacteria, and also more effective on the S. aureus biofilm production than the others.

13.
Appl Radiat Isot ; 148: 191-196, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30978655

RESUMO

Tungsten-188 (t1/2 = 69.4 d) is routinely produced by double neutron capture using highly enriched 186W target, 186W(n,γ)187W(n,γ)188W reaction, at the ORNL 85 MWt High Flux Isotope Reactor. While the thermal neutron cross section for the first reaction, 186W(n,γ)187W, is well known, the single reported 64 b cross-section for the second reaction, 187W(n,γ)188W, cannot be validated by experimental results that yield lower than expected activities of 188W. In this study, we report a new value for the thermal neutron capture cross section of 187W. After confirming the neutron capture cross section of 186W (σ0 = 37.8 ±â€¯1.8 b for thermal and I0 = 476 ±â€¯25 b for resonance integrals with σ0/I0 = 12.6 ±â€¯0.4) in two short irradiations, longer irradiations (1-10 d) were performed to obtain a value of 6.5 ±â€¯0.8 b for the σ0 of 187W, which is lower than the adopted value by a factor of 10. Due to the short half-life of 187W (t1/2 = 23.7 d), the σ0 for 187W was obtained empirically by comparing the 188W experimental yields with the theoretical yields generated by code IsoChain and varying the 187W cross section while keeping all other parameters constant.

14.
Photodiagnosis Photodyn Ther ; 26: 361-365, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31026614

RESUMO

Tri-tert-butyl-carboxyl subphthalocyanine (SubPc) was synthesized and evaluated as a fluorescence agent. Fluorescence imaging for breast tumor in vivo was performed using nude mice as models. Results indicate high uptake in tumor at 20 h. Tumor-non tumor ratio was determined as 2.25. The imaging results demonstrate the potential of this fluorescence-imaging agent in the diagnosis of breast tumor. In the future, subphthalocyanine is also developing as a dual functional, which is fluorescence imaging and as a photodynamic therapeutic agent for the treatment and diagnosis of cancer.


Assuntos
Indóis/farmacologia , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Imagem Óptica/métodos , Fármacos Fotossensibilizantes/farmacologia , Animais , Feminino , Indóis/síntese química , Isoindóis , Camundongos , Camundongos Nus , Fármacos Fotossensibilizantes/síntese química
15.
Appl Biochem Biotechnol ; 187(4): 1539-1550, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30276529

RESUMO

Snake venoms are a natural biological source that has potential therapeutic value with various protein compounds. Disintegrins originally were discovered as a family of proteins from snake venoms composed of cysteine rich low molecular weight polypeptides. Disintegrins exhibit specific binding and higher affinity toward integrin with potential inhibition of function. Trans-membrane receptors of the integrin family may involve in many pathological conditions such as inflammation and tumor progression with important processes related to invasion and migration. Since disintegrins have the ability to bind to integrins, they could be used for cancer detection and treatment, and in monitoring of therapy in select cancer types. The main purpose of the study is to investigate disintegrin containing Vipera anatolica (VAT) crude venom potential for radiolabeling and intracellular uptake as well as electrochemical biosensing assay against U87MG human brain glioblastoma cells. For this purpose, VAT crude venom containing U87MG cell-specific disintegrin was investigated in terms of radiolabeling and intracellular uptake as well as electrochemical biosensing assay in comparison with echistatin (ECT) disintegrin in cells. The interaction between VAT crude venom and ECT with HEK293 human non-tumorigenic embryonic kidney cells and glioblastoma U87MG cells was electrochemically investigated using pencil graphite electrodes (PGEs). The interaction of the VAT crude venom and ECT with HEK293 and U87MG cells was detected according to the changes in oxidation signals. Then, VAT crude venom and echistatin were labeled with 131I via iodogen method. Intracellular uptakes of radiolabeled molecules were investigated in U87MG cell line. 131I-VAT can be an agent for imaging of glioblastoma cancer. Further work will focus on the production of large quantities of pure VAT disintegrin with a biotechnological approach to improving imaging agent.


Assuntos
Técnicas Biossensoriais , Desintegrinas/metabolismo , Espaço Intracelular/metabolismo , Venenos de Serpentes/metabolismo , Viperidae , Animais , Linhagem Celular Tumoral , Eletroquímica , Humanos , Marcação por Isótopo , Transporte Proteico
16.
Molecules ; 23(11)2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30355983

RESUMO

BACKGROUND: Photodynamic therapy (PDT) is a non-invasive and innovative cancer therapy based on the photodynamic effect. In this study, we sought to determine the singlet oxygen production, intracellular uptake, and in vitro photodynamic therapy potential of Cetixumab-targeted, zinc(II) 2,3,9,10,16,17,23,24-octa(tert-butylphenoxy))phthalocyaninato(2-)-N29,N30,N31,N32 (ZnPcOBP)-loaded mesoporous silica nanoparticles against pancreatic cancer cells. RESULTS: The quantum yield (ΦΔ) value of ZnPcOBP was found to be 0.60 in toluene. In vitro cellular studies were performed to determine the dark- and phototoxicity of samples with various concentrations of ZnPcOBP by using pancreatic cells (AsPC-1, PANC-1 and MIA PaCa-2) and 20, 30, and 40 J/cm² light fluences. No dark toxicity was observed for any sample in any cell line. ZnPcOBP alone showed a modest photodynamic activity. However, when incorporated in silica nanoparticles, it showed a relatively high phototoxic effect, which was further enhanced by Cetuximab, a monoclonal antibody that targets the Epidermal Growth Factor Receptor (EGFR). The cell-line dependent photokilling observed correlates well with EGFR expression levels in these cells. CONCLUSIONS: Imidazole-capped Cetuximab-targeted mesoporous silica nanoparticles are excellent vehicles for the selective delivery of ZnPcOBP to pancreatic cancer cells expressing the EGFR receptor. The novel nanosystem appears to be a suitable agent for photodynamic therapy of pancreatic tumors.


Assuntos
Cetuximab/farmacologia , Indóis/administração & dosagem , Nanopartículas , Compostos Organometálicos/administração & dosagem , Fármacos Fotossensibilizantes/administração & dosagem , Dióxido de Silício , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Cetuximab/química , Humanos , Indóis/química , Isoindóis , Luz , Nanopartículas/química , Compostos Organometálicos/química , Neoplasias Pancreáticas , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Porosidade , Dióxido de Silício/química , Oxigênio Singlete/química , Compostos de Zinco
17.
Chem Biol Drug Des ; 91(6): 1094-1100, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29363273

RESUMO

Ampicillin is a one of effective antibiotics against Gram-positive and Gram-negative bacteria. This study aimed to label ampicillin-loaded graphene oxide nanoflake (AMP-GO) with 99m Tc and evaluate of its in vitro binding to Staphylococcus aureus and Escherichia coli. Firstly, ampicillin was loaded into graphene oxide nanoflake prepared. AMP-GO was characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM) techniques, and the amount of loaded ampicillin onto GO was determined by UV-Vis absorption spectroscopy. AMP and AMP-GO were labeled with 99m Tc using stannous chloride reducing agent. Labeling efficiency of 99m Tc-AMP-GO was found to be 97.66 ± 2.06%. 99m Tc-AMP-GO has higher binding efficiencies to both S. aureus and E. coli than 99m Tc-AMP. 99m Tc-AMP-GO could be promising candidate as agent infection nuclear imaging. Furthermore, in vivo studies of 99m Tc-AMP-GO with infected rats are planned to be performed.


Assuntos
Ampicilina/química , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Grafite/química , Nanoestruturas/química , Staphylococcus aureus/efeitos dos fármacos , Ampicilina/farmacologia , Antibacterianos/química , Portadores de Fármacos/química , Marcação por Isótopo , Compostos de Organotecnécio/química , Espectroscopia de Infravermelho com Transformada de Fourier
18.
Chem Biol Drug Des ; 91(3): 789-796, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29136341

RESUMO

In recent years, phthalocyanines (Pcs) have been widely used as photosensitizer in photodynamic therapy applications. Because of their strong absorptions in the near-infrared region (640-700 nm). The integration of phthalocyanine derivatives to a nanoparticle is expected to be efficient way to improve the activity of the photosensitizer on the targeted tissue. It is known that the integrated molecules not only show better accumulation on tumor tissue but also reduce toxicity in healthy tissues. In this study, the ZnPc molecule was synthesized and integrated to the TiO2 nanoparticle, to investigate the potential of PDT and its cytotoxicity. Additionally, ZnPc and ZnPc-TiO2 molecules were labeled with 131 I and it was aimed to put forth the nuclear imaging/therapy potentials of 131 I labeled ZnPc/ZnPc-TiO2 by determining in vitro uptakes in mouse mammary carcinoma (EMT6), human cervical adenocarcinoma (HeLa). In result of our study, it was observed that the radiolabeling yields of the synthesized ZnPc and ZnPc-TiO2 with 131 I were quite high. In vitro uptake studies shown that 131 I-ZnPc-TiO2 could be a potential agent for nuclear imaging/treatment of breast and cervical cancers. According to PDT results, ZnPc-TiO2 might have as to be a potential PDT agent in the treatment of cervical tumor. ZnPc and ZnPc-TiO2 might be used as theranostic agents.


Assuntos
Indóis , Imageamento por Ressonância Magnética , Neoplasias Mamárias Animais , Nanopartículas , Fotoquimioterapia , Titânio , Neoplasias do Colo do Útero , Zinco , Animais , Feminino , Células HeLa , Humanos , Indóis/química , Indóis/farmacologia , Isoindóis , Neoplasias Mamárias Animais/diagnóstico por imagem , Neoplasias Mamárias Animais/tratamento farmacológico , Neoplasias Mamárias Animais/metabolismo , Camundongos , Nanopartículas/química , Nanopartículas/uso terapêutico , Titânio/química , Titânio/farmacologia , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo , Zinco/química , Zinco/farmacologia
19.
Int J Pharm ; 524(1-2): 467-474, 2017 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-28365390

RESUMO

Phthalocyanines (Pcs) are commonly used as Photosensors (PSs) in Photodynamic Therapy (PDT) applications due to their intense absorption in the far red-near IR spectral region with a high extinction coefficient and high ability for generating singlet oxygen. Pcs targetspecifically tumors, and do not show any considerable toxic effects under the absence of light. In particular, their chemical versatility has allowed the introducion a number of substituent at the periferal or axial positions which provide modulating photophysical properties, increases the solubility of these compounds in organic solvents. Nanoparticles increase the bioavailability, stability, and transport of PSs to target tissue. TiO2 nanoparticles are prefered in these applications because of their non toxic, low cost and high chemical stability properties. In our study, a Zinc Phthalocyanine (ZnPc) was used as a photosensor. The design of ZnPc integrated TiO2 nanoparticles is intended to make PSs a more effective PDT agent. With the aim to examine the nuclear imaging/treatment potentials of ZnPc and ZnPc-TiO2 in hepatocellular carcinoma (HepG2), colorectal adenocarcinoma (HT29) tumor and human healthy lung (WI38) cell lines in vitro study ZnPc and TiO2-ZnPc were also labeled with 131I. It is determined that 131I-ZnPc-TiO2 nanoparticle show a potential as an agent for the imaging/treatment of hepatocellular cancer by in vitro. The toxicity studies revealed that TiO2 nanoparticle decreases the toxicity of ZnPc. In vitro PDT results show that TiO2-ZnPc has a potential as a PDT agent in colon tumor treatment. Consequently, synthesized ZnPc and ZnPc-TiO2 could be promising candidates as theranostic agents.


Assuntos
Indóis/química , Nanopartículas/química , Compostos Organometálicos/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Titânio/química , Linhagem Celular Tumoral , Células HT29 , Células Hep G2 , Humanos , Isoindóis , Compostos de Zinco
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