Nanoparticle-Cell Interactions: Surface Chemistry Effects on the Cellular Uptake of Biocompatible Block Copolymer Assemblies.

The development of nanovehicles for intracellular drug delivery is strongly bound to the understating and control of nanoparticles cellular uptake process, which in turn is governed by surface chemistry. In this study, we explored the synthesis, characterization, and cellular uptake of block copolymer assemblies consisting of a pH-responsive poly[2-(diisopropylamino)ethyl methacrylate] (PDPA) core stabilized by three different biocompatible hydrophilic shells (a zwitterionic type poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) layer, a highly hydrated poly(ethylene oxide) (PEO) layer with stealth effect, and an also proven nontoxic and nonimmunogenic poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) layer). All particles had a spherical core-shell structure. The largest particles with the thickest hydrophilic stabilizing shell obtained from PMPC40-b-PDPA70 were internalized to a higher level than those smaller in size and stabilized by PEO or PHPMA and produced from PEO122-b-PDPA43 or PHPMA64-b-PDPA72, respectively. Such a behavior was confirmed among different cell lines, with assemblies being internalized to a higher degree in cancer (HeLa) as compared to healthy (Telo-RF) cells. This fact was mainly attributed to the stronger binding of PMPC to cell membranes. Therefore, cellular uptake of nanoparticles at the sub-100 nm size range may be chiefly governed by the chemical nature of the stabilizing layer rather than particles size and/or shell thickness.

Improved anti-inflammatory properties of xanthan gum hydrogel physically and chemically modified with yeast derived peptide.

Bioactive peptides from natural resources with associated beneficial biological properties such as skin wound healing have drawn much attention. Polysaccharides with their biocompatibility, biodegradability, and ease of modification are suitable carriers for peptides delivery to the wound. In this study, a polysaccharide-peptide system was designed for potential wound healing applications. Xanthan hydrogels were modified with the yeast-derived peptide VW-9 with known biological properties via chemical conjugation using carbodiimide chemistry (XG-g-VW-9) or physically incorporation (XG-p-VW-9). Grafting VW-9 to the hydrogels increased the hydrogels' swelling degree and the release of the peptide from the hydrogels followed the Higuchi model indicating the peptide diffusion from the hydrogel matrix without hydrogel matrix dissolution. Both hydrogels were cytocompatible toward the tested fibroblast and macrophage cells. XG-p-VW-9 and XG-g-VW-9 reduce the level of tumor necrosis factor-alpha and interleukin-6 in cells activated with lipopolysaccharide more efficiently than free VW-9. Thus, VW-9-modified xanthan hydrogels may have the potential to be considered for skin wound healing.

Sweet Vector for Gene Delivery: the Sugar Decoration of Polyplexes Reduces Cytotoxicity with a Balanced Effect on Gene Expression.

The use of sugar-functionalized polyplexes as a nonviral gene delivery vector with lower cytotoxicity than the well-known polymeric carrier branched polyethyleneimine (BPEI) is investigated. The substitution of primary amine groups in the BPEI chains with lactose residues leads to larger polyplexes, presumably due to the higher amount of polymer required to complete DNA condensation. Nevertheless, the sugar functionalization substantially reduces the cytotoxicity of the assemblies. The nanocomplexes are taken up by the cells to a greater extent, whereas the levels of gene expression are maintained compared to those obtained using BPEI, which is known for its excellent transfection efficiency. Accordingly, the preparation of lower-cytotoxicity polyplexes while maintaining gene expression, which is highly relevant to the field, is demonstrated.