Cellular response to nanoscale elastin-like polypeptide polyelectrolyte multilayers.

Ionic elastin-like polypeptide (ELP) conjugates are a new class of biocompatible, self-assembling biomaterials. ELPs composed of the repeat unit (GVGVP)(n) are derived from the primary sequence of mammalian elastin and produced in Escherichia coli. These biopolymers exhibit an inverse transition temperature that renders them extremely useful for applications in cell-sheet engineering. Cationic and anionic conjugates were synthesized by the chemical coupling of ELP to polyethyleneimine (PEI) and polyacrylic acid (PAA). The self-assembly of ELP-PEI and ELP-PAA using the layer-by-layer deposition of alternately charged polyelectrolytes is a simple, versatile technique to generate bioactive and biomimetic surfaces with the ability to modulate cell-substratum interactions. Our studies are focused on cellular response to self-assembled multilayers of ionic (GVGVP)(40) incorporated within the polymeric sequence H(2)N-MVSACRGPG-(GVGVP)(40)-WP-COOH. Angle-dependent XPS studies indicated a difference in the chemical composition at the surface ( approximately 10A below the surface) and subsurface regions. These studies provided additional insight into the growth of the nanoscale multilayer assembly as well as the chemical environment that the cells can sense. Overall, cellular response was enhanced on glass substrata coated with ELP conjugates compared with uncoated surfaces. We report significant differences in cell proliferation, focal adhesions and cytoskeletal organization as a function of the number of bilayers in each assembly. These multilayer assemblies have the potential to be successfully utilized in the rational design of coatings on biomaterials to elicit a desired cellular response.

Polysaccharide-based nanoparticles for theranostic nanomedicine.

Polysaccharides are natural biological molecules that have numerous advantages for theranostics, the integrated approach of therapeutics and diagnostics. Their derivable reactive groups can be leveraged for functionalization with a nanoparticle-enabling conjugate, therapeutics (small molecules, proteins, peptides, photosensitizers) and/or diagnostic agents (imaging agents, sensors). In addition, polysaccharides are diverse in size and charge, biodegradable and abundant and show low toxicity in vivo. Polysaccharide-based nanoparticles are increasingly being used as platforms for simultaneous drug delivery and imaging and are therefore becoming popular theranostic nanoparticles. The review focuses on the method of nanoparticle formation (self-assembled, physical or chemical cross-linked) when engineering polysaccharide-based nanoparticles for theranostic nanomedicine. We highlight recent examples of polysaccharide-based theranostic systems from literature and their potential for use in the clinic, particularly chitosan- and hyaluronic acid-based NPs.