One of the mechanisms responsible for cancer-induced increased blood supply in malignant neoplasms is the overexpression of vascular endothelial growth factor (VEGF). Several antibodies for VEGF targeting have been produced for both imaging and therapy. Molecularly imprinted polymer nanoparticles, nanoMIPs, however, offer significant advantages over antibodies, in particular in relation to improved stability, speed of design, cost and control over functionalization. In the present study, the successful production of nanoMIPs against human VEGF is reported for the first time. NanoMIPs were coupled with quantum dots (QDs) for cancer imaging. The composite nanoparticles exhibited specific homing toward human melanoma cell xenografts, overexpressing hVEGF, in zebrafish embryos. No evidence of this accumulation was observed in control organisms. These results indicate that nanoMIPs are promising materials which can be considered for advancing molecular oncological research, in particular when antibodies are less desirable due to their immunogenicity or long production time.
Controlling neuronal cell adhesion, migration, and axonal outgrowth via contact interactions with biomaterials is a critical element for tissue engineering applications and for developing artificial neuronal interfaces. One promising approach relies on the exploitation of nanostructured surfaces. Here, the human neuroblastoma cell line SH-SY5Y is interfaced with plastic nanogratings (NGs; anisotropic topographies composed by alternating lines of grooves and ridges with sub-micrometer lateral dimension). The SH-SY5Y cells' (SHs) contact guidance is investigated under proliferating conditions and upon differentiation after treatment with retinoic acid (RA) and brain-derived neurotrophin factor (BDNF), and compared with mouse primary hippocampal neurons (HNs). Quantitative readouts are obtained by measuring changes in tubulin cytoskeleton organization and cell morphology induced by mechanotransduction. Results demonstrate that SHs effectively retrieve substrate topographical signals, in particular during differentiation. Remarkably, RA/BDNF improves SH responsiveness to NG directional cues, and significantly enhances the alignment to the NG lines. HNs behave similarly, showing a marked change in network organization if cultured on NGs. These results might help the rational engineering of neuro-regenerative scaffolds to improve peripheral nerve wound healing, as well as to investigate the basic mechanisms of neuronal wiring.
The use of antibodies (Abs) and enzymes in diagnostic assays is widely accepted and, to date, represents the gold standard in terms of sensitivity and affinity. Abs are routinely used in many diagnostic assays but they suffer from short shelf-life, high costs of manufacturing and relatively poor stability, especially at extremes of temperature and pH. The use of molecularly imprinted polymer (MIP) nanoparticles can overcome these problems. Compared with Abs, the synthesis of MIPs is simpler and more cost-effective and, moreover, does not require involvement of animals. In addition, MIPs show high stability and excellent mechanical properties, and can be prepared virtually for any target. NanoMIPs, sometimes called ″plastic antibodies″, are nanostructured polymer particles capable of selectively recognising the said target. Thanks to their size, they represent a viable alternative to Abs, as demonstrated by their recent application in several diagnostic fields. Herein, we review the most common synthetic approaches in the manufacture of nanoMIPs, together with some recent examples of the use of nanoMIPs in diagnostics, in particular within sensors, assays and for imaging purposes.
The conversion of proliferating skeletal muscle precursors (myoblasts) to terminally-differentiated myocytes is a critical step in skeletal muscle development and repair. We show that EphA7, a juxtacrine signaling receptor, is expressed on myocytes during embryonic and fetal myogenesis and on nascent myofibers during muscle regeneration in vivo. In EphA7-/- mice, hindlimb muscles possess fewer myofibers at birth, and those myofibers are reduced in size and have fewer myonuclei and reduced overall numbers of precursor cells throughout postnatal life. Adult EphA7-/- mice have reduced numbers of satellite cells and exhibit delayed and protracted muscle regeneration, and satellite cell-derived myogenic cells from EphA7-/- mice are delayed in their expression of differentiation markers in vitro. Exogenous EphA7 extracellular domain will rescue the null phenotype in vitro, and will also enhance commitment to differentiation in WT cells. We propose a model in which EphA7 expression on differentiated myocytes promotes commitment of adjacent myoblasts to terminal differentiation.
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