Danyang Li

Superparamagnetic iron oxide nanoparticles for MR imaging and therapy: design considerations and clinical applications.

Superparamagnetic iron oxide nanoparticles (SPION) based magnetic resonance imaging (MRI) is a powerful non-invasive tool in biomedical imaging, clinical diagnosis and therapy. In this review, the physicochemical properties of SPION and their in vivo performance were thoroughly discussed, also covering how surface engineering will prolong the circulation time and overcome biological barriers at organ, tissue, and cellular levels. Clinical applications and future potentials of SPION based MR imaging in cancer, cardiovascular, and inflammation diseases were addressed. Targeting mechanisms of SPION in both research and clinical use were summarized for better understanding of their performance. Addition of new targeting mechanisms to clinically approved SPION will bring opportunities to discover early diseases at cellular and molecular levels, and to track MRI-visible drug carriers. Clinical trial information related to SPION on Clinicaltrials.gov was summarized mainly based on their disease categories, therapeutic applications and clinical trial stages. It gives us a brief outlook of their clinical applications in the near future.

Adhesive ligand tether length affects the size and length of focal adhesions and influences cell spreading and attachment

Cells are known to respond to physical cues from their microenvironment such as matrix rigidity. Discrete adhesive ligands within flexible strands of fibronectin connect cell surface integrins to the broader extracellular matrix and are thought to mediate mechanosensing through the cytoskeleton-integrin-ECM linkage. We set out to determine if adhesive ligand tether length is another physical cue that cells can sense. Substrates were covalently modified with adhesive arginylglycylaspartic acid (RGD) ligands coupled with short (9.5u2009nm), medium (38.2u2009nm) and long (318u2009nm) length inert polyethylene glycol tethers. The size and length of focal adhesions of human foreskin fibroblasts gradually decreased from short to long tethers. Furthermore, we found cell adhesion varies in a linker length dependent manner with a remarkable 75% reduction in the density of cells on the surface and a 50% reduction in cell area between the shortest and longest linkers. We also report the interplay between RGD ligand concentration and tether length in determining cellular spread area. Our findings show that without varying substrate rigidity or ligand density, tether length alone can modulate cellular behaviour.

Multivalent manganese complex decorated amphiphilic dextran micelles as sensitive MRI probes

T1 contrast agents based on Mn(II) were conjugated on amphiphilic dextran micelles via click chemistry. The obtained paramagnetic nanomicelle contrast agent has a higher T1 relaxivity (13.3 Mn mmol-1 s-1) and better sensitivity than those of free Mn(II) complexes. Studies carried out in vivo suggest that this contrast agent has a better and long-acting vascular enhancement effect at a lower manganese dosage (0.1 Mn mmol kg-1 BW).

Failure mechanisms in denture adhesives

OBJECTIVEnThe mechanical properties of bio adhesives in oral care application are expected to be critical in defining the stability and release of devices such as dentures from the oral tissue. A multiscale experimental mechanical approach is used to evaluate the performance of denture adhesive materials.nnnMETHODSnThe inherent mechanical behavior of denture fixatives was examined by separating adhesive material from a representative polymethyl methacrylate (PMMA) surface using atomic force microscopy (AFM) approaches and compared to macroscopic mechanical testing.nnnRESULTSnFailure of denture adhesive material was found to be critically dependent on the formation of fibrillar structures within the adhesive. Small scale mechanical testing provided evidence for the mechanical properties of the fibrillar structures formed within the adhesive in macroscopic mechanical testing and indicated the importance of the forces required to fail the adhesive at these small length scales in controlling both the maximum forces sustained by the bulk material as well as the ease of separating the adhesive from PMMA surfaces.nnnSIGNIFICANCEnOur results are important in defining the performance of denture fixative materials and their control of adhesive behavior, allowing the potential to tune properties required in the adhesion and removal of dentures.

In-situ NIR-laser mediated bioactive substance delivery to single cell for EGFP expression based on biocompatible microchamber-arrays

&NA; Controlled drug delivery and gene expression is required for a large variety of applications including cancer therapy, wound healing, cell migration, cell modification, cell‐analysis, reproductive and regenerative medicine. Controlled delivery of precise amounts of drugs to a single cell is especially interesting for cell and tissue engineering as well as therapeutics and has until now required the application of micro‐pipettes, precisely placed dispersed drug delivery vehicles, or injections close to or into the cell. Here we present surface bound micro‐chamber arrays able to store small hydrophilic molecules for prolonged times in subaqueous conditions supporting spatiotemporal near infrared laser mediated release. The micro‐chambers (MCs) are composed of biocompatible and biodegradable polylactic acid (PLA). Biocompatible gold nanoparticles are employed as light harvesting agents to facilitate photothermal MC opening. The degree of photothermal heating is determined by numerical simulations utilizing optical properties of the MC, and confirmed by Brownian motion measurements of laser‐irradiated micro‐particles exhibiting similar optical properties like the MCs. The amount of bioactive small molecular cargo (doxycycline) from local release is determined by fluorescence spectroscopy and gene expression in isolated C2C12 cells via enhanced green fluorescent protein (EGFP) biosynthesis. Graphical abstract Laser mediated release of small hydrophilic molecule doxycycline from biodegradable and biocompatible surface bound microchambers arrays is demonstrated by controlled EGFP expression of a targeted cell in a cell colony. Figure. No caption available.

Solution Conformation of Polymer Brushes Determines Their Interactions with DNA and Transfection Efficiency

Polymer brush-functionalized nanomaterials offer interesting features for the design of gene delivery vectors as their physicochemical and structural properties can be designed independently of the chemistry, size and shape of the nanomaterial core. However, little is known of the parameters regulating the adsorption and infiltration of DNA molecules at the surface of positively charged polymer brushes, despite the importance of such processes for gene delivery. Here we investigate the role of the molecular environment (e.g., pH, type of buffer, concentration) on the interactions between plasmid DNA and positively charged poly(dimethylaminoethyl methacrylate) (PDMAEMA) brushes using a combination of light scattering, electrophoretic light scattering, in situ ellipsometry, and surface plasmon resonance. We show that the conformation of swollen PDMAEMA brushes is modulated by the surrounding buffer and that this impacts strongly on the ability of such brushes and nanomaterials based on these coatings to complex DNA molecules. In turn, the levels of transfection efficiency measured correlate with changes in brush conformation and DNA binding. Therefore, this work demonstrates the importance of molecular design of polymer brushes to control DNA complexation and release in order to optimize the performance of polymer brush-functionalized nanomaterials for gene delivery applications.

Highly Stable RNA Capture by Dense Cationic Polymer Brushes for the Design of Cytocompatible, Serum-Stable SiRNA Delivery Vectors

The high density of polymer brushes confers to these coatings unique physicochemical properties, in particular for the regulation of biomolecular interaction and the design of highly selective coatings for biosensors and protein patterning. Here, we show that high density poly(dimethylaminoethyl methacrylate) cationic polymer brushes enable the stable uptake of high levels of oligonucleotides. This is proposed to result from the high degree of crowding and associated increase in entropic driving force for the binding of polyelectrolytes such as nucleic acid molecules. We further demonstrate the ease with which such coatings allow the design of highly structured nanomaterials for siRNA delivery using block copolymer-brush-based nanoparticles that allow the protection of oligonucleotides by a protein-resistant outer block. In particular, these nanomaterials display a high serum stability and low cytotoxicity while retaining excellent knock down efficiencies. Polymer brush-based nanomaterials therefore appear particularly attractive for the rational design of a new generation of high performance theranostics and RNA delivery probes.