RESUMO
Angiogenesis inhibitor drugs have been explored as important pharmacological agents for cancer therapy, including hepatocellular carcinoma. These agents have several drawbacks, such as drug resistance, nonspecific toxicity, and systemic side effects. Therefore, combination therapy of the drug and small interfering RNA could be a promising option to achieve high therapeutic efficacy while allowing a lower systemic dose. Therefore, we studied adding an alpha-fetoprotein siRNA (AFP-siRNA) incorporated on polymeric nanoparticles (NPs) along with angiogenesis inhibitor drugs. The AFP siRNA-loaded NPs were successfully synthesized at an average size of 242.00 ± 2.54 nm. Combination treatment of AFP-siRNA NPs and a low dose of sunitinib produced a synergistic effect in decreasing cell viability in an in vitro hepatocellular carcinoma (HCC) model. AFP-siRNA NPs together with sorafenib or sunitinib greatly inhibited cell proliferation, showing only 39.29 ± 2.72 and 44.04 ± 3.05% cell viability, respectively. Moreover, quantitative reverse transcription PCR (qRT-PCR) demonstrated that AFP-siRNA incorporated with NPs could significantly silence AFP-mRNA expression compared to unloaded NPs. Interestingly, the expression level of AFP-mRNA was further decreased to 28.53 ± 5.10% when sunitinib was added. Therefore, this finding was considered a new promising candidate for HCC treatment in reducing cell proliferation and enhancing therapeutic outcomes.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , RNA Interferente Pequeno/uso terapêutico , alfa-Fetoproteínas/genética , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Sunitinibe/uso terapêutico , Linhagem Celular Tumoral , Polímeros/uso terapêutico , RNA MensageiroRESUMO
OBJECTIVE: The aim of this study was to develop a composite scaffold with the optimal poly(lactic-co-glycolic acid) (PLGA) and bioactive glass proportions to provide an environment for bone tissue regeneration and repair. DESIGN: PLGA-bioactive glass composite scaffolds were prepared using a salt-leaching technique with different percentages of bioactive glass (0%, 10 %, and 15 % [w/w]) with PLGA. The resulting scaffolds were characterized using scanning electron microscopy and energy dispersive X-ray spectroscopy (SEM-EDS), and water contact angle, dynamic mechanical, and pH analysis. The scaffold biocompatibility was investigated using stem cells from human exfoliated deciduous teeth (SHED) and rat experiments. RESULTS: SEM-EDS confirmed the successful fabrication of three-dimensional PLGA-bioactive glass scaffolds. The results showed that 10 % bioactive glass with PLGA exhibited favorable properties including increased pore size, hydrophilicity, and mechanical properties. The growth medium pH was increased for scaffolds containing bioactive glass. All scaffolds were biocompatible, and 10 % bioactive glass composite scaffolding showed better attachment, growth, and proliferation of SHED compared to the other scaffolds. Moreover, it enhanced osteogenic differentiation of SHED in vitro and in vivo. CONCLUSIONS: Salt-leaching-derived PLGA-bioactive glass composite scaffolds were successfully established. PLGA with 10 % bioactive glass had adequate physical properties and bioactivity, and it could be considered as a composite for bone tissue engineering applications.
