RESUMO
OBJECTIVE: In the present work, we report for the first time the therapeutic potential of talazoparib (BMN 673)-SLNs for the treatment of BRCA1 deficient Triple Negative Breast Cancer (TNBC). BMN 673-SLNs were produced by hot-homogenization technique and then characterized. METHODS: The cytotoxic and apoptotic effects of BMN 673-SLNs compared with BMN 673 were determined on HCC1937BRCA1-/-, HCC1937-R resistant TNBC and MCF-10A control cell lines. BMN 673- SLNs were found to have reduced particle size (219.5 ± 1.45 nm) and thus more stable (-28.4 ± 2.52 mV) than BMN 673 (1652 ± 2.46 nm and -18.6 ± 0.45 mV) at 4°C. RESULTS: In vitro cell line studies demonstrated that BMN 673-SLNs showed significant cytotoxic effects on HCC1937 (29.8%) and HCC1937-R cells (35.7%) at 10 nM for 12 days compared with BMN 673 (HCC1937 cells: 34.0% and HCC1937-R cells: 93.8% at 10 nM for 12 days) (p<0.05). Additionally, BMN 673-SLNs (40.1%) reduced the toxicity of BMN 673 (53.1%) on MCF-10A control cells thanks to unique physical properties. CONCLUSION: The apoptotic rates in the 10 nM BMN 673-SLNs treatment (88.78% and 85.56%) for 12 days were significantly higher than those in 10 nM BMN 673 (82.6% and 25.86%) for 12 days in HCC1937 and HCC1937-R cells, respectively (p<0.01). Furthermore, these effects were consistent with the findings of colony formation, wound healing and calcein accumulation analysis. In conclusion, the therapeutic potential of BMN 673-SLNs provides a promising chemotherapeutic strategy for the treatment of drugresistant TNBC.
Assuntos
Antineoplásicos/farmacologia , Proteína BRCA1/antagonistas & inibidores , Lipídeos/química , Nanopartículas/química , Ftalazinas/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proteína BRCA1/deficiência , Proteína BRCA1/metabolismo , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Ftalazinas/química , Relação Estrutura-Atividade , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Células Tumorais CultivadasRESUMO
The objective of the present study was to investigate the effect of tamoxifen (Tam) loaded solid lipid nanoparticles (SLNs) on MCF7 Tam-resistant breast cancer cells (MCF7-TamR). Tam-SLNs were produced by the hot homogenization method. The characterization studies of Tam-SLNs demonstrated good physical stability with small particle size. The in vitro cytotoxicity results showed that Tam-SLNs enhanced the efficacy of Tam and reversed the acquired Tam resistance by inducing apoptosis, altering the expression levels of specific miRNA and the related apoptosis-associated target-genes in both MCF7 and MCF7-TamR cells without damaging the MCF10A control cells (pâ¯<â¯0.05). In conclusion, we demonstrated a molecular mechanism of the induction of apoptosis by Tam-SLNs in MCF7 and MCF7-TamR cells, and thus, we demonstrated that Tam-SLNs were more effective than Tam. The present study suggests that the use SLNs may be a potential therapeutic strategy to overcome Tam-resistance in breast cancer for clinical use.
Assuntos
Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/tratamento farmacológico , Portadores de Fármacos , Resistencia a Medicamentos Antineoplásicos , Lipídeos/química , Nanopartículas , Tamoxifeno/farmacologia , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/química , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Composição de Medicamentos , Estabilidade de Medicamentos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , MicroRNAs/genética , MicroRNAs/metabolismo , Nanotecnologia , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Tamoxifeno/administração & dosagem , Tamoxifeno/química , Tecnologia Farmacêutica/métodos , Fatores de TempoRESUMO
Malignant pleural mesothelioma (MPM), the incidence increased with each passing day, is an important lethal disease due to the limited survive with available treatment methods and with the lack of a standard treatment. Response and survive rates of cytotoxic agents which is used in MPM treatment are not good enough. Therefore, treatment studies of MPM seem to quite important and urgent. In cancer therapy, convensional chemotherapeutic agent applications, due to the lack of selectivity, lead to systemic toxicity. Besides the limited solubility of the agent used, the distribution between the cells is weak. It is very difficult to the pass through cellular barriers, particularly, drug resistance may develop to the treatment. All of these reasons lead to failure in the treatment process. Because of the fact that cytotoxic drugs either kill the rapidly growing and dividing cells or make them disfunctional by showing toxic effect on them, to avoid the side effects and to make an inherent effect for cytotoxic drug of active ingredient given for treatment on tumor, different studies have been under investigation. At the present time, nanocarriers as one of these solutions seem to have an important place. Nanocarriers are promising for the development of therapeutic effectiveness and safety. It seems that use of the nanocarrier in the treatment of mesothelioma has a potential, as effective alternative a method, with improve of the drug efficacy and reduce of toxicity in normal tissues.
Assuntos
Antineoplásicos/administração & dosagem , Portadores de Fármacos , Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Nanotecnologia/instrumentação , Neoplasias Pleurais/tratamento farmacológico , Humanos , Mesotelioma MalignoRESUMO
Recent studies have focused on the potential use of metal-based complexes for the treatment of cancer. However, there are some limitations of metal-based ligands for the treatment of cancer due to their toxic effects. In the present study, a novel bimetallic Cu(II) complex, [Cu2(µ-(C6H5)2CHCOO)3 (bipy)2)](ClO4), has firstly been synthesized and characterized by FT-IR, and X-ray crystallography. Furthermore, Cu(II) complex-loaded solid lipid nanoparticles (SLNs) were initially prepared by hot homogenization method to overcome their toxic effects. After characterization, comparative cytotoxic and apoptotic activities of the complex and Cu(II) complex-SLNs on human breast cancer cells (MCF-7) and human umbilical vein endothelial cells (HUVEC) were determined. Cu(II) complex demonstrated considerable in vitro cytotoxic effects on MCF-7 (p<0.05) and induced apoptotic cell death (88.02 ± 3.95%) of MCF-7 cells. But, the complex has also toxic effects (69.5%) on HUVEC control cells. For this purpose, Cu(II) complex-loaded solid lipid nanoparticles (SLN) were firstly produced, with a distrubution range of 190±1.45 nm to 350±1.72 nm and zeta potentials of -27.4±1.98 mV and -18.2±1.07 mV, respectively. The scanning electron microscopy (SEM) images of SLNs were also obtained. In vitro studies have shown that Cu(II) complex-SLNs help in reducing the side effect of Cu(II) complex (29.9%) on HUVEC control cells. Therefore, metal based complex might potentially be used for cancer treatment through nanoparticle based drug delivery systems.
Assuntos
Antineoplásicos/administração & dosagem , Cobre/administração & dosagem , Portadores de Fármacos/administração & dosagem , Nanopartículas/administração & dosagem , Compostos Organometálicos/administração & dosagem , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cobre/química , Portadores de Fármacos/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Lipídeos/administração & dosagem , Lipídeos/química , Células MCF-7 , Nanopartículas/química , Compostos Organometálicos/químicaRESUMO
Many anticancer drugs that are currently used in cancer treatment are natural products or their analogues by structural modification. Caffeic acid (3, 4-dihydroxycinnamic acid; CA) is classified as hydroxycinnamic acid and has a variety of potential pharmacological effects, including antioxidant, immunomodulatory and anti-inflammatory activities. As a drug carrier, solid lipid nanoparticles (SLNs) introduced to improve stability, provide controlled drug release, avoid organic solvents and are obtained in small sizes. In this study, we developed solid lipid nanoparticles incorporating with caffeic acid using hot homogenization method. Caffeic acid loaded solid lipid nanoparticles were characterized regarding particle size, zeta potential, drug entrapment efficiency, drug release, scanning electron microscopy (SEM) and FT-IR. The effects of caffeic acid loaded solid lipid nanoparticles on MCF-7 cells were determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-dimethyl tetrazolium bromide (MTT) test and Annexin V-PI analysis. As a result, solid lipid nanoparticles could potentially be used for the delivery of caffeic acid and solid lipid nanoparticles formulation enhanced the effects of caffeic acid on MCF-7 cells. Some relevant patents are also referred in this article.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Ácidos Cafeicos/farmacologia , Lipídeos/química , Antineoplásicos/administração & dosagem , Neoplasias da Mama/patologia , Ácidos Cafeicos/administração & dosagem , Química Farmacêutica , Preparações de Ação Retardada , Portadores de Fármacos/química , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Células MCF-7 , Microscopia Eletrônica de Varredura , Nanopartículas , Tamanho da Partícula , Patentes como Assunto , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Nocodazole (NCD) has more carcinogenic effect than similar drugs. Moreover, it has low drug release time and high particle size. Solid Lipid Nanoparticles (SLNs) have been evaluated for decrease in particle size and therefore increase in drug release time, for such drugs. In this study, NCD has been successfully incorporated into SLNs systems and remained stable for a period of 90 days. NCD structure related to the chemical nature of solid lipid is a key factor to decide whether anticarcinogenic agent will be incorporated in the long term and for a controlled optimization of active ingredient incorporation and loading, intensive characterization of the physical state of the lipid particles were highly essential. Thus, NMR, FT-IR, DSC (for thermal behavior) analyses were performed and the results did not indicate any problem on stability. Moreover, SLNs were decreased size of NCD in addition to increase in time of the drug release. After SLN preparation, particle size, polydispersity index, electrical conductivity and zeta potential were measured and drug release from NCD-loaded SLNs were performed. These values seem to be of the desired range.