One of the greatest challenges in cell therapy is to minimally invasively deliver a large quantity of viable cells to a tissue of interest with high engraftment efficiency. Low and inefficient homing of systemically delivered mesenchymal stem cells (MSCs), for example, is thought to be a major limitation of existing MSC-based therapeutic approaches, caused predominantly by inadequate expression of cell surface adhesion receptors. Using a platform approach that preserves the MSC phenotype and does not require genetic manipulation, we modified the surface of MSCs with a nanometer-scale polymer construct containing sialyl Lewisx (sLex) that is found on the surface of leukocytes and mediates cell rolling within inflamed tissue. The sLex engineered MSCs exhibited a robust rolling response on inflamed endothelium in vivo and homed to inflamed tissue with higher efficiency compared with native MSCs. The modular approach described herein offers a simple method to potentially target any cell type to specific tissues via the circulation.
Through targeted binding to the cell membrane, structural DNA nanotechnology has the potential to guide and affix biomolecules such as drugs, growth factors and nanobiosensors to the surfaces of cells....
Nucleic acid-based materials enable sub-nanometer precision in self-assembly for fields including biophysics, diagnostics, therapeutics, photonics, and nanofabrication. However, structural DNA nanotechnology has been limited to substantially hydrated media. Transfer to organic solvents commonly used in polymer and peptide synthesis results in the alteration of DNA helical structure or reduced thermal stabilities. Here we demonstrate that gammamodified peptide nucleic acids (γPNA) can be used to enable formation of complex, selfassembling nanostructures in select polar aprotic organic solvent mixtures. However, unlike the diameter-monodisperse populations of nanofibers formed using analogous DNA approaches, γPNA structures appear to form bundles of nanofibers. A tight distribution of the nanofiber diameters could, however, be achieved in the presence of the surfactant SDS during self-assembly. We further demonstrate nanostructure morphology can be tuned by means of solvent solution and by strand substitution with DNA and unmodified PNA. This work thereby introduces a science of γPNA nanotechnology.
The evergrowing need to understand and engineer biological and biochemical mechanisms has led to the emergence of the field of nanobiosensing. Structural DNA nanotechnology, encompassing methods such as DNA origami and single-stranded tiles, involves the base pairing-driven knitting of DNA into discrete one-, two-, and three-dimensional shapes at nanoscale. Such nanostructures enable a versatile design and fabrication of nanobiosensors. These systems benefit from DNA's programmability, inherent biocompatibility, and the ability to incorporate and organize functional materials such as proteins and metallic nanoparticles. In this review, we present a mix-and-match taxonomy and approach to designing nanobiosensors in which the choices of bioanalyte and transduction mechanism are fully independent of each other. We also highlight opportunities for greater complexity and programmability of these systems that are built using structural DNA nanotechnology. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Diagnostic Tools > Biosensing Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.
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