Liver cancer cells: targeting and prolonged-release drug carriers consisting of mesoporous silica nanoparticles and alginate microspheres

A new microsphere consisting of inorganic mesoporous silica nanoparticles (MSNs) and organic alginate (denoted as MSN@Alg) was successfully synthesized by air-dynamic atomization and applied to the intracellular drug delivery systems (DDS) of liver cancer cells with sustained release and specific targeting properties. MSN@Alg microspheres have the advantages of MSN and alginate, where MSN provides a large surface area for high drug loading and alginate provides excellent biocompatibility and COOH functionality for specific targeting. Rhodamine 6G was used as a model drug, and the sustained release behavior of the rhodamine 6G-loaded MSN@Alg microspheres can be prolonged up to 20 days. For targeting therapy, the anticancer drug doxorubicin was loaded into MSN@Alg microspheres, and the (lysine)4-tyrosine-arginine-glycine-aspartic acid (K(4)YRGD) peptide was functionalized onto the surface of MSN@Alg for targeting liver cancer cells, hepatocellular carcinoma (HepG2). The results of the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and confocal laser scanning microscopy indicate that the MSN@Alg microspheres were successfully uptaken by HepG2 without apparent cytotoxicity. In addition, the intracellular drug delivery efficiency was greatly enhanced (ie, 3.5-fold) for the arginine-glycine-aspartic acid (RGD)-labeled, doxorubicin-loaded MSN@Alg drug delivery system compared with the non-RGD case. The synthesized MSN@Alg microspheres show great potential as drug vehicles with high biocompatibility, sustained release, and targeting features for future intracellular DDS

Fabrication and Application of Iron(III)-Oxide Nanoparticle/Polydimethylsiloxane Composite Cone in Microfluidic Channels

This paper presented the fabrication and applications of an iron(III)-oxide nanoparticle/polydimethylsiloxane (PDMS) cone as a component integrated in lab on a chip. The two main functions of this component were to capture magnetic microbeads in the microfluid and to mix two laminar fluids by generating disturbance. The iron(III)-oxide nanoparticle/PDMS cone was fabricated by automatic dispensing and magnetic shaping. Three consecutive cones of 300 μm in height were asymmetrically placed along a microchannel of 2 mm in width and 1.1 mm in height. Flow passing the cones was effectively redistributed for Renolds number lower than . Streptavidin-coated magnetic microbeads which were bound with biotin were successfully captured by the composite cones as inspected under fluorescence microscope. The process parameters for fabricating the composite cones were investigated. The fabricated cone in the microchannel could be applied in lab on a chip for bioassay in the future

Sternness and transdifferentiation of adipose-derived stem cells using L-ascorbic acid 2-phosphate-induced cell sheet formation

Cell sheet technology has emerged as an important tissue engineering approach. Adipose-derived stem cells (ASCs) have valuable applications in regenerative medicine, but their sternness and differentiation capabilities in the cell sheet format have not been well investigated. In this study, we found that L-ascorbate 2-phosphate (A2-P), a stable form of ascorbic acid, significantly enhanced ASC proliferation and induced ASC sheet fabrication in 7 days with abundant extracellular matrix deposition. Importantly, A2-P treatment significantly enhanced expression of pluripotent markers Sox-2, Oct-4 and Nanog, but treating ASCs with antioxidants other than A2-P revealed no sternness enhancement. Moreover, ASC treatment with A2-P and a collagen synthesis inhibitor, L-2-azetidine carboxylic acid or cis-4-hydroxy-D-proline, significantly inhibited the A2-P-enhanced expression of sternness markers. These findings demonstrated that A2-P enhances sternness of ASCs through collagen synthesis and cell sheet formation. We also showed that A2-P-stimulated collagen synthesis in ASCs may be mediated through ERK1/2 pathway. By culturing the ASC sheets in proper induction media, ASC transdifferentiation capabilities into neuron and hepatocyte-like cells were significantly enhanced after cell sheet formation, while adipogenic and osteogenic differentiation capacities were still maintained. Using a murine model of healing-impaired cutaneous wound, faster wound healing was noted in the group that received ASC sheet treatment, and we observed significantly more engrafted ASCs with evidence of differentiation toward endothelial and epidermal lineages in the cutaneous wound tissue. Therefore, A2-P-mediated ASC sheet formation enhanced ASC sternness and transdifferentiation capabilities, thereby representing a promising approach for applications in regenerative medicine. (C) 2014 Elsevier Ltd. All rights reserved