No abstract

Herein, we present a straightforward synthesis of pH-responsive chitosan-capped mesoporous silica nanoparticles (MSNs). These MCM-41-type MSNs could be used as nanocapsules to accommodate guest molecules. Subsequently, (3-glycidyloxypropyl)trimethoxysilane was grafted onto the surface of the MSNs, which served as a bridge to link between MSNs and chitosan, which is ubiquitous in nature and commercially available. Owing to the pH-responsive and biocompatible features of chitosan, the loading and release of an anti-cancer drug, doxorubicin hydrochloride, were carried out in vitro, in which the composite chitosan-capped MSNs (CS-MSNs) showed excellent environmental response. As the pH value of the media decreased, the degree of drug release correspondingly increased. Moreover, thanks to the perfect biocompatibility of chitosan, the CS-MSNs exhibited lower cytotoxicity than that of the naked MSNs in an MTT assay. In addition, the in vitro kill potency against MCF-7 breast-cancer cells was enhanced over time, as well as with increasing concentration of the drug-loaded CS-MSNs. These results indicate that CS-MSNs are promising candidates for pH-responsive drug delivery in cancer therapy.

R8 photoreceptor cells play a primary role in the differentiation of Drosophila eyes. In scabrous (sca) mutants, the pattern of R8 photoreceptor differentiation is altered. The sca gene is predicted to encode a secreted protein related in part to fibrinogen and tenascins. Using expression in Drosophila Schneider cells, we showed that sca encoded a dimeric glycoprotein which was secreted and found in soluble form in the tissue culture medium. The sca protein contained both N-and O-linked carbohydrates and interacted with heparin. This Schneider cell protein was similar to protein detected in embryos. We showed that sca mutations, along with conditional alleles of Notch (N) and Delta (Dl), each affected the pattern of cells expressing atonal (ato), the proneural gene required for R8 differentiation. In normal development, about 1 cell in 20 differentiates into an R8 cell; in the others, ato is repressed. N and Dl were required to repress ato in the vicinity of R8 cells, whereas sca had effects over several cell diameters. Certain antibodies detected uptake of sca protein several cells away from its source. The overall growth factor-like structure of sca protein, its solubility, and its range of effects in vivo are consistent with a diffusible role that complements mechanisms involving direct cell contact. We propose that as the morphogenic furrow advances, cells secreting sca protein control the pattern of the next ommatidial column.Cell-cell signals mediated both by diffusible factors and by direct cell contact are thought to be important during development. Studies of the Drosophila eye have contributed examples of interactions between neighboring cells (49). Definitive proofs of diffusible signaling have been harder to obtain. Here we have characterized the scabrous protein, a candidate secreted signal acting in eye development.The Drosophila retina is made up of hundreds of 20-cell ommatidia, precisely arranged in a hexagonal array. The origin of the array during development is not fully understood. As the wave of differentiation crosses the eye imaginal disc from posterior to anterior, the ommatidia in each new column form out of phase with those in the previous column. Within each ommatidium, R8 photoreceptor cells are the first cell type to differentiate, and each R8 cell is required for differentiation of the other ommatidial cells. R8 cell determination is thus important for the entire retinal pattern (24,33,43).Several lines of evidence suggest that determination of the R8 cells shares features with determination of neural cells from undifferentiated ectoderm in other parts of the nervous system. R8 differentiation requires the basic helix-loop-helix protein atonal (ato), similar to the proneural genes required for other neural cells (24). Loss of Notch (N) or Delta (Dl) gene function results in supernumerary R8 cells, similar to the neural hypertrophy that these neurogenic mutations cause elsewhere (3, 5, 32). Retinal differentiation is delayed by the helixloop-helix genes hairy and extramacrochaetae, a...

No abstract