RESUMO
Aim: To synthesize HER2 aptamer-conjugated iron oxide nanoparticles with a coating of poly(2-(dimethylamino) ethyl methacrylate)-poly(2-methacryloyloxyethylphosphorylcholine) block copolymer (IONPPPs). Methods: Characterization covered molecular structure, chemical composition, thermal stability, magnetic characteristics, aptamer interaction, crystalline nature and microscopic features. Subsequent investigations focused on IONPPPs for in vitro cancer cell identification. Results: Results demonstrated high biocompatibility of the diblock copolymer with no significant toxicity up to 150 µg/ml. The facile coating process yielded the IONPP complex, featuring a 13.27 nm metal core and a 3.10 nm polymer coating. Functionalized with a HER2-targeting DNA aptamer, IONPPP enhanced recognition in HER2-amplified SKBR3 cells via magnetization separation. Conclusion: These findings underscore IONPPP's potential in cancer research and clinical applications, showcasing diagnostic efficacy and HER2 protein targeting in a proof-of-concept approach.
Assuntos
Neoplasias da Mama , Nanopartículas , Nylons , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Polímeros/química , Metacrilatos/química , Nanopartículas Magnéticas de Óxido de Ferro , Nanopartículas/químicaRESUMO
From the point of view of classical electrodynamics, nano-optical and enantioselective tweezers for single biomolecules have been routinely investigated using achiral and chiral localized surface plasmons, respectively. In this work, we propose the use of interference of collective plasmons (Fano-type plasmon) that exist in densely hexagonal plasmonic oligomers to design a high-efficiency nano-optical tweezer to trap individual biomolecules with a radius of 2 nm. For this purpose, we fabricated and simulated 2D hexagonal arrays of Au nanoparticles (AuNPs) with sub-wavelength lattice spacing which support collective plasmons by near-field coupling. Our full-field simulations show that densely hexagonal plasmonic oligomers can enhance the Fano-like resonances arising from the interference of superradiant and subradiant modes. This interference of collective plasmons results in a strong intensification and localization of the electric near-field in the interstice of the AuNPs. The methodology can also be extended to collective chiral near-fields for all-optical enantioseparation of chiral biomolecules with a small chirality parameter (±0.001) with the hypothesis of the existence of strong magnetic near-fields.
RESUMO
Caffeine (CAF) is a psychostimulant present in many beverages and with rapid bioabsorption. For this reason, matrices that effectuate the sustained release of a low amount of CAF would help reduce the intake frequency and side effects caused by high doses of this stimulant. Thus, in this study, CAF was loaded into magnetic gelatin/alginate (Gel/Alg/MNP) hydrogels at 18.5 mg/ghydrogel. The in vitro release of CAF was evaluated in the absence and presence of an external magnetic field (EMF) and Ca2+. In all cases, the presence of Ca2+ (0.002 M) retarded the release of CAF due to favorable interactions between them. Remarkably, the release of CAF from Gel/Alg/MNP in PBS/CaCl2 (0.002 M) at 37 °C under an EMF was more sustained due to synergic effects. In PBS/CaCl2 (0.002 M) and at 37 °C, the amounts of CAF released after 45 min from Gel/Alg and Gel/Alg/MNP/EMF were 8.3 ± 0.2 mg/ghydrogel and 6.1 ± 0.8 mg/ghydrogel, respectively. The concentration of CAF released from Gel/Alg and Gel/Alg/MNP hydrogels amounted to ~0.35 mM, thereby promoting an increase in cell viability for 48 h. Gel/Alg and Gel/Alg/MNP hydrogels can be applied as reservoirs to release CAF at suitable concentrations, thus forestalling possible side effects and improving the viability of SH-SY5Y cells.
RESUMO
Magnetic responsive hydrogels composed of alginate (Alg) and xanthan gum (XG), crosslinked with Ca2+ ions, were modified by in situ magnetic nanoparticles (MNP) formation. In comparison to magnetic Alg hydrogels, magnetic Alg-XG hydrogels presented superior mechanical and swelling properties, due to the high charge density and molecular weight of XG. The loading efficiency of levodopa (LD), an important antiparkinson drug, in the Alg-XG/MNP hydrogels was the highest (64%), followed by Alg/MNP (56%), Alg-XG (53%) and Alg (28%). A static external magnetic field (EMF) of 0.4â¯T stimulated the release of LD from Alg-XG/MNP hydrogels achieving 64⯱â¯6% of the initial loading after 30â¯h. The viability, proliferation and expression of dopaminergic markers of human neuroblastoma SH-SY5Y cell on the LD loaded magnetic hydrogels were successful, particularly under EMF, which stimulated the release of LD. Overall, the results of this study provided the rational design of magnetic hydrogels for the delivery of drugs, which combined with external magnetic stimulus, might improve cell proliferation and specific differentiation.
Assuntos
Hidrogéis/química , Levodopa/química , Campos Magnéticos , Magnetismo , Alginatos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dopaminérgicos/administração & dosagem , Dopaminérgicos/química , Dopaminérgicos/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Humanos , Concentração de Íons de Hidrogênio , Levodopa/administração & dosagem , Levodopa/farmacocinética , Microscopia Eletrônica de Varredura , Polissacarídeos Bacterianos/químicaRESUMO
Magnetic scaffolds with different charge densities were prepared using magnetic nanoparticles (MNP) and xanthan gum (XG), a negatively charged polysaccharide, or hydroxypropyl methylcellulose (HPMC), an uncharged cellulose ether. XG chains were crosslinked with citric acid (cit), a triprotic acid, whereas HPMC chains were crosslinked either with cit or with oxalic acid (oxa), a diprotic acid. The scaffolds XG-cit, HPMC-cit and HPMC-oxa were characterized by scanning electron microscopy (SEM), inductively coupled plasma atomic emission spectroscopy (ICP-AES), superconducting quantum interference device (SQUID) magnetometry, contact angle and zeta-potential measurements. In addition, the flux of Ca2+ ions through the scaffolds was monitored by using a potentiometric microsensor. The adhesion and proliferation of murine fibroblasts (NIH/3T3) on XG-cit, XG-cit-MNP, HPMC-cit, HPMC-cit-MNP, HPMC-oxa and HPMC-oxa-MNP were evaluated by MTT assay. The magnetic scaffolds presented low coercivity (<25Oe). The surface energy values determined for all scaffolds were similar, ranging from 43mJm-2 to 46mJm-2. However, the polar component decreased after MNP incorporation and the dispersive component of surface energy increased in average 1mJm-2 after MNP incorporation. The permeation of Ca2+ ions through XG-cit-MNP was significantly higher in comparison with that on XG-cit and HPMC-cit scaffolds, but through HPMC-cit-MNP, HPMC-oxa and HPMC-oxa-MNP scaffolds it was negligible within the timescale of the experiment. The adhesion and proliferation of fibroblasts on the scaffolds followed the trend: XG-cit-MNP>XG-cit>HPMC-cit, HPMC-cit-MNP, HPMC-oxa, HPMC-oxa-MNP. A model was proposed to explain the cell behavior stimulated by the scaffold charge, MNP and Ca2+ ions permeation.
Assuntos
Cálcio/metabolismo , Derivados da Hipromelose/farmacologia , Campos Magnéticos , Nanopartículas de Magnetita/química , Polissacarídeos Bacterianos/farmacologia , Alicerces Teciduais/química , Animais , Cálcio/química , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Derivados da Hipromelose/química , Íons/química , Íons/metabolismo , Camundongos , Estrutura Molecular , Células NIH 3T3 , Polissacarídeos Bacterianos/químicaRESUMO
Hybrid beads composed of magnetite nanoparticles (MNP) and alginate (Alg) were synthesized and coded as Alg-MNP. They were incubated in dopamine (DOPA) solution (5 g/L), at pH 7.4 and 8 °C, during 12 h, promoting the DOPA loaded magnetic beads, coded as Alg-MNP/DOPA. The release of DOPA was further evaluated in the absence and the presence of external magnetic field (EMF) of 0.4 T. The products Alg-MNP and Alg-MNP/DOPA were characterized by scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS), Fourier transform infrared vibrational spectroscopy (FTIR), UV spectrophotometry, thermogravimetric analyses (TGA), inductively coupled plasma atomic emission spectroscopy (ICP-AES) analyses and superconducting quantum interference device (SQUID) magnetometer. The magnetic and chemical properties of Alg-MNP beads were not affected by DOPA loading. The incorporation of DOPA into the beads depended on the pH and on the negative charge density. At pH 7.4 38% of DOPA were loaded into Alg-MNP beads, whereas at pH 2 or using neat Alg beads (lower charge density than Alg-MNP) the loading efficiency decreased to one third or less. In the absence of EMF, 24% of the loaded DOPA was released from Alg-MNP at pH 7.4 over a period of 26 h. The released amount increased to 33% under the stimulus of EMF. A model was proposed to explain the loading efficiency of charged drugs, as DOPA, into hybrid beads and the role played by EMF on delivery systems, where drug and matrix are oppositely charged. The results suggest that the alginate combined with magnetite nanoparticles is a promising system for release of DOPA in the presence of EMF.
Assuntos
Alginatos/química , Dopamina/química , Óxido Ferroso-Férrico/química , Nanopartículas de Magnetita/química , Microesferas , Algoritmos , Dopamina/farmacocinética , Dopaminérgicos/química , Dopaminérgicos/farmacocinética , Liberação Controlada de Fármacos , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Concentração de Íons de Hidrogênio , Cinética , Campos Magnéticos , Nanopartículas de Magnetita/ultraestrutura , Microscopia Eletrônica de Varredura , Estrutura Molecular , Espectrometria por Raios X , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Hybrid scaffolds made of xanthan and magnetite nanoparticles (XCA/mag) were prepared by dipping xanthan membranes (XCA) into dispersions of magnetic nanoparticles for different periods of time. The resulting hybrid scaffolds presented magnetization values ranging from 0.25 emu g(-1) to 1.80 emu g(-1) at 70 kOe and corresponding iron contents ranging from 0.25% to 2.3%, respectively. They were applied as matrices for in vitro embryoid body adhesion and neuronal differentiation of embryonic stem cells; for comparison, neat XCA and commercial plastic plates were also used. Adhesion rates were more pronounced when cells were seeded on XCA/mag than on neat XCA or plastic dishes; however, proliferation levels were independent from those of the scaffold type. Embryonic stem cells showed similar differentiation rates on XCA/mag scaffolds with magnetization of 0.25 and 0.60 emu g(-1), but did not survive on scaffolds with 1.80 emu g(-1). Differentiation rates, expressed as the number of neurons obtained on the chosen scaffolds, were the largest on neat XCA, which has a high density of negative charge, and were smallest on the commercial plastic dishes. The local magnetic field inherent of magnetite particles present on the surface of XCA/mag facilitates synapse formation, because synaptophysin expression and electrical transmission were increased when compared to the other scaffolds used. We conclude that XCA/mag and XCA hydrogels are scaffolds with distinguishable performance for adhesion and differentiation of ESCs into neurons.