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Microenvironmental factors play critical roles in regulating stem cell fate, providing a rationale to engineer biomimetic microenvironments that facilitate rapid and effective stem cell differentiation. Three-dimensional (3D) hierarchical microarchitectures have been developed to enable rapid neural differentiation of multipotent human mesenchymal stromal cells (HMSCs) via mechanotransduction. However, low cell viability during long-term culture and poor cell recovery efficiency from the architectures were also observed. Such problems hinder further applications of the architectures in stem cell differentiation. Here, we present improved 3D nanostructured microarchitectures functionalized with cell-adhesion-promoting arginylglycylaspartic acid (RGD) peptides. These RGD-functionalized architectures significantly upregulated long-term cell viability and facilitated effective recovery of differentiated cells from the architectures while maintaining high differentiation efficiency. Efficient recovery of highly viable differentiated cells enabled the downstream analysis of morphology and protein expression to be performed. Remarkably, even after the removal of the mechanical stimulus provided by the 3D microarchitectures, the recovered HMSCs showed a neuron-like elongated morphology for 10 days and consistently expressed microtubule-associated protein 2, a mature neural marker. RGD-functionalized nanostructured microarchitectures hold great potential to guide effective differentiation of highly viable stem cells.

A new strategy for designing contrast agents (CAs) based on geometrical confinement will become a competent way to improve the relaxivity of CAs. Herein, a magnetic resonance imaging (MRI) nanoconstruct is fabricated through loading Gd2O3 nanoparticles into mesoporous carbon nanospheres, followed by conjugation of poly(ethylene glycol) (PEG) and the c(RGDyK) peptide (Gd2O3@OMCN-PEG-RGD), which could prolong the blood circulation half-life as well as improve the tumor-targeting ability. As a result, the Gd2O3@OMCN-PEG-RGD exhibits an outstandingly high relaxivity (r1 = 68.02 mM–1 s–1), which is ∼5.3 times higher than that of Gd2O3 nanoparticles (r1 = 12.74 mM–1 s–1). Afterward, both the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test and H&E staining show that the Gd2O3@OMCN-PEG-RGD has wonderful biocompatibility in vitro and in vivo. Moreover, the in vivo MR images indicate that the Gd2O3@OMCN-PEG-RGD could accumulate in the tumor region more rapidly than Gd2O3@OMCN-PEG. This study prese...

Chemotherapy of bladder cancer has limited efficacy because of the short retention time of drugs in the bladder during therapy. In this research, nanoparticles (NPs) with a new core/shell/corona nanostructure have been synthesized, consisting of iron oxide (Fe3O4) as the core to providing magnetic properties, drug (doxorubicin) loaded calcium phosphate (CaP) as the shell for pH-responsive release, and arginylglycylaspartic acid (RGD)-containing peptide functionalized alginate as the corona for cell targeting (with the composite denoted as RGD-Fe3O4/CaP/Alg NPs). We have optimized the reaction conditions to obtain RGD-Fe3O4/CaP/Alg NPs with high biocompatibility and suitable particle size, surface functionality, and drug loading/release behavior. The results indicate that the RGD-Fe3O4/CaP/Alg NPs exhibit enhanced chemotherapy efficacy toward T24 bladder cancer cells, owing to successful magnetic guidance, pH-responsive release, and improved cellular uptake, which give these NPs great potential as therapeu...

Disintegrins are potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion. A new disintegrin, salmosin, isolated from the venom of the Korean snake Agkistrodon halys brevicaudus, has been characterized by mass spectrometry and NMR spectroscopy, and its in vitro biological activity has been assessed. The IC(50) value of the purified salmosin was determined to be 2.2 nM in an assay for the inhibition of glycoprotein IIb-IIIa/fibrinogen interaction. Salmosin also inhibited the bovine capillary endothelial cell proliferation induced by bFGF in a dose-dependent manner. The NMR solution structures were well converged with a root-mean-square deviation of 0.76 A for backbone atoms among the 20 lowest energy structures, except for the arginylglycylaspartic acid (RGD) loop. The structure revealed that the conserved RGD motif with an unusual finger shape is distal from the rigid core of the C-terminal domain. Furthermore, even though the RGD motif did not interact with the hydrophobic core of the protein, it was stabilized by a network of molecular contacts through a small antiparallel beta-sheet comprising residues of Ile46-Ala50 and Asp54-Tyr58. Last, the electrostatic charge distribution on the surface of salmosin differs dramatically from that of other disintegrin proteins in that there is a cluster of negatively charged residues in close proximity to the RGD loop.