ABSTRACT
Biomimicry strategies, inspired from natural organization of living organisms, are being widely used in the design of nanobiomaterials. Particularly, nonlithographic techniques have shown immense potential in the facile fabrication of nanostructured surfaces at large-scale production. Orthopedic biomaterials or coatings possessing extracellular matrix-like nanoscale features induce desirable interactions between the bone tissue and implant surface, also known as osseointegration. In this study, nanopillared chitosan/gelatin (C/G) films were fabricated using nanoporous anodic alumina molds, and their antibacterial properties as well as osteogenesis potential were analyzed by comparing to the flat C/G films and tissue culture polystyrene as controls. In vitro analysis of the expression of RUNX2, osteopontion, and osteocalcin genes for mesenchymal stem cells as well as osteoblast-like Saos-2 cells was found to be increased for the cells grown on nano C/G films, indicating early-stage osteogenic differentiation. Moreover, the mineralization tests (quantitative calcium analysis and alizarin red staining) showed that nanotopography significantly enhanced the mineralization capacity of both cell lines. This work may provide a new perspective of biomimetic surface topography fabrication for orthopedic implant coatings with superior osteogenic differentiation capacity and fast bone regeneration potential.
ABSTRACT
Antisense oligonucleotide (ASO)-conjugated-α-tocopherol succinate (TCS)-loaded-poly(lactic acid)-g-poly(ethylene glycol) nanoparticles (ASO-TCS-PLA-PEG NPs), with the ratio of polymer/TCS of 10:2.5, 10:5, 10:7 (w/w) were prepared for targeting cancer therapy. The amphiphilic PLA, amino terminated PEG graft copolymers were synthesized by ring opening polymerization reaction. Nanoparticles were produced by using double emulsion (w/o/w) solvent evaporation method. ASO-TCS-PLA-PEG NPs demonstrated satisfactory encapsulation and loading efficiency and size distribution. The short-term stability studies were carried out at 4 and 25 °C for 30 days to assess their mean particle size, polydispersity index and zeta potential. The cellular uptake and extended cytoplasmic retention of the NPs in A549 human lung carcinoma and L929 mouse fibroblast cells were examined by fluorescence and confocal microscopy. In human lung cancer cells, ASO-TCS-PLA-PEG NPs exhibited better cellular internalization, cytotoxicity and apoptotic and necrotic effects compared to healthy cell line, L929. These findings showed that ASO-modified nanoparticles could serve as a promising nanocarrier for targeted tumor cells.
