RESUMEN
The development of functional nanocarriers that can enhance the cellular delivery of a variety of nucleic acid agents is important in many biomedical applications such as siRNA therapy. We report the synthesis of large pore mesoporous silica nanoparticles (LPMSN) loaded with iron oxide and covalently modified by polyethyleneimine (denoted PEI-Fe-LPMSN) as carriers for gene delivery. The LPMSN have a particle size of â¼200 nm and a large pore size of 11 nm. The large pore size is essential for the formation of large iron oxide nanoparticles to increase the magnetic properties and the adsorption capacity of siRNA molecules. The magnetic property facilitates the cellular uptake of nanocarriers under an external magnetic field. PEI is covalently grafted on the silica surface to enhance the nanocarriers' affinity against siRNA molecules and to improve gene silencing performance. The PEI-Fe-LPMSN delivered siRNA-PLK1 effectively into osteosarcoma cancer cells, leading to cell viability inhibition of 80%, higher compared to the 50% reduction when the same dose of siRNA was delivered by a commercial product, oligofectamine.
Asunto(s)
Técnicas de Transferencia de Gen , Nanopartículas de Magnetita/química , Dióxido de Silicio/química , Adsorción , Transporte Biológico Activo , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Terapia Genética/métodos , Humanos , Nanopartículas de Magnetita/administración & dosificación , Nanopartículas de Magnetita/ultraestructura , Nanotecnología , Oligodesoxirribonucleótidos/administración & dosificación , Oligodesoxirribonucleótidos/farmacocinética , Osteosarcoma/enzimología , Osteosarcoma/genética , Osteosarcoma/terapia , Polietileneimina/química , Porosidad , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/genética , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/farmacocinética , Quinasa Tipo Polo 1RESUMEN
Novel silica nanoparticles mimicking virus surface topography are prepared. It is demonstrated that increases in nanoscale surface roughness promote both binding of biomolecules and cellular uptake; thus, the cellular delivery efficiency is significantly increased (scale bars 20â µm).
Asunto(s)
Portadores de Fármacos/química , Nanopartículas/química , Dióxido de Silicio/química , Materiales Biocompatibles/química , Materiales Biocompatibles/metabolismo , Carbocianinas/química , Carbocianinas/metabolismo , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/toxicidad , Células HeLa , Humanos , Células MCF-7 , Microscopía Confocal , Nanopartículas/toxicidad , Oligonucleótidos/química , Oligonucleótidos/metabolismo , Polietileneimina/química , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Propiedades de Superficie , Proteínas de Unión al GTP rab/antagonistas & inhibidores , Proteínas de Unión al GTP rab/genética , Proteínas de Unión al GTP rab/metabolismo , Quinasa Tipo Polo 1RESUMEN
Delicate α-Fe2O3 multi-shelled hollow spheres have been prepared by a simple and scalable spray drying method followed by annealing in air. The resulting material shows high specific capacity, good cycling stability, and excellent rate performance in lithium ion battery applications.
RESUMEN
Large pore mesoporous silica nanoparticles (LP-MSNs) functionalized with poly-L-lysine (PLL) were designed as a new carrier material for gene delivery applications. The synthesized LP-MSNs are 100-200 nm in diameter and are composed of cage-like pores organized in a cubic mesostructure. The size of the cavities is about 28 nm with an entrance size of 13.4 nm. Successful grafting of PLL onto the silica surface through covalent immobilization was confirmed by X-ray photoelectron spectroscopy, solid-state (13)C magic-angle spinning nuclear magnetic resonance, Fourier transformed infrared, and thermogravimetric analysis. As a result of the particle modification with PLL, a significant increase of the nanoparticle binding capacity for oligo-DNAs was observed compared to the native unmodified silica particles. Consequently, PLL-functionalized nanoparticles exhibited a strong ability to deliver oligo DNA-Cy3 (a model for siRNA) to Hela cells. Furthermore, PLL-functionalized nanoparticles were proven to be superior as gene carriers compared to amino-functionalized nanoparticles and the native nanoparticles. The system was tested to deliver functional siRNA against minibrain-related kinase and polo-like kinase 1 in osteosarcoma cancer cells. Here, the functionalized particles demonstrated great potential for efficient gene transfer into cancer cells as a decrease of the cellular viability of the osteosarcoma cancer cells was induced. Moreover, the PLL-modified silica nanoparticles also exhibit a high biocompatibility, with low cytotoxicity observed up to 100 µg/mL.