RESUMEN
Nanostructure arrays have drawn much attention and are promising as new biomaterials in the field of biomedicine. In recent years, numerous experimental studies on the cell behavior of nanostructured arrays (NSs) have been published, describing a wide variety of experimental results. But there are only a few theoretical analyses that elucidate the mechanisms of interactions between cells and nanostructures. Here we present a quantitative thermodynamic model to elucidate the effects of surface topography of nanostructure arrays on cell adhesion. Based on the established model, we studied the equilibrium state of cell adhesion by analyzing the change in free energy during the adhesion process. Theoretical results showed that cell adhesion mode is actually determined by the balance between adhesion energy and deformation energy of the cell membrane. According to the calculated results, a phase diagram of the cell adhesion has been constructed, which can clarify the interrelated effects of the radius and surface distribution density of nanopillars. We can identify the relation between the surface topography of nanostructure arrays and the cell adhesion mode from the phase.
Asunto(s)
Materiales Biocompatibles/química , Adhesión Celular , Nanoestructuras/química , Membrana Celular/química , Simulación por Computador , Tamaño de la Partícula , Teoría Cuántica , Propiedades de Superficie , TermodinámicaRESUMEN
Chemodynamic therapy (CDT) is a highly tumor-specific treatment, while its efficacy is compromised by the intratumoral Fenton reaction efficiency, which is determined by the following reaction factors, including the availability of Fenton ions (e.g., Fe2+), the amount of H2O2, and the degree of acidity. Synchronous optimization of these factors is a big challenge for efficient CDT. Herein, a strategy of comprehensively optimizing Fenton reaction factors was developed for traceable multistage augmented CDT by charge-reversal theranostics. The customized pH-responsive poly(ethylene)glycol-poly(ß-amino esters) (PEG-PAE) micelle (PM) was prepared as the carrier. Glucose oxidase (GOx), Fe2+, and pH-responsive second near-infrared (NIR-II) LET-1052 probe were coloaded by PM to obtain the final theranostics. The activity of metastable Fe2+ remained by the unsaturated coordination with PEG-PAE. Then tumor accumulation and exposure of Fe2+ were achieved by charge-reversal cationization of PEG-PAE, which was further enhanced by a GOx catalysis-triggered pH decrease. Together with the abundant H2O2 generation and pH decrease through GOx catalysis, the limiting factors of the Fenton reaction were comprehensively optimized, achieving the enhanced CDT both in vitro and in vivo. These findings provide a strategy for comprehensively optimizing intratumoral Fenton reaction factors to overcome the intrinsic drawbacks of current CDT.
Asunto(s)
Peróxido de Hidrógeno , Medicina de Precisión , Catálisis , Ésteres , Glucosa OxidasaRESUMEN
Zinc oxide (ZnO) nanostructures have been widely studied in biomedical fields due to their special properties. In recent years, ZnO spherical nanoparticles (SNPs) with nano-size as an anti-tumor agent have been widely concerned. While the effects of the non-spherical shaped ZnO nanoparticles on tumor cell death have been rarely reported. Here, we prepared ZnO spiky nanoparticles (SPNPs) as the research subject. We found that the SPNPs showed superiority in killing tumor cells. To be specific, SPNPs presented a long-term cytotoxicity effect on killing tumor cells, as plenty of SPNPs retained on the cell plasma membrane's exterior and still showed toxicity effect on tumor cells after co-incubation multiple times. Moreover, compared to SNPs, it was encouraging that SPNPs still showed stronger cytotoxicity in both simulated circulatory systems of tumor cells and 3D tumor cell spheroids. The stronger toxicity against tumor cells suggested that ZnO SPNPs have more advantages on killing tumor cells as a promising nanomedicine.