A poly(amide)-based dendrimer was synthesized and functionalized with the membrane-interacting peptide gH(625-644) (gH625) derived from the herpes simplex virus type 1 (HSV-1) envelope glycoprotein H, which has previously been shown to assist in delivering large cargoes across the cellular membrane. We demonstrate that the attachment of the gH625 peptide sequence to the termini of a dendrimer allows the conjugate to penetrate into the cellular matrix, whereas the unfunctionalized dendrimer is excluded from translocation. The peptide-functionalized dendrimer is rapidly taken into the cells mainly through a non-active translocation mechanism. Our results suggest that the presented peptidodendrimeric scaffold may be a promising material for efficient drug delivery.

Development of elaborate three-dimensional multivalent displays appended on natural or synthetic molecular scaffolds.

First-and second-generation Newkome-type dendronized norbornene macromonomers were synthesized and polymerized by ringopening metathesis polymerization (ROMP). In the case of the second-generation macromonomer, the rate of polymerization was highly dependent on the initial concentration of the macromonomer; quasi-quantitative polymerization was only achieved when the concentration was higher than 50 mM. Adding a linker between the polymerizable group and the dendron increased the rate of polymerization and it was possible to reach quantitative conversions at lower concentration. Doubling the length of the linker further improved the polymerization to a rate comparable with the polymerization of the first-generation dendronized macromonomer. The dendronized polymers presented herein consist of a poly(amide)-based dendron attached to the poly(norbornene) backbone. Because of the properties of these components such as biocompatibility, we foresee these polymers having possible applications in therapeutics.

Polymer-protein conjugates are biohybrid macromolecules derived from covalently connecting synthetic polymers with polypeptides. The resulting materials combine the properties of both worlds: chemists can engineer polymers to stabilize proteins, to add functionality, or to enhance activity; whereas biochemists can exploit the specificity and complexity that Nature has bestowed upon its macromolecules. This has led to a wealth of applications, particularly within the realm of biomedicine. Polymer-protein conjugation has expanded to include scaffolds for drug delivery, tissue engineering, and microbial inhibitors. This feature article reflects upon recent developments in the field and discusses the applications of these hybrids from a biomaterials standpoint.

A biodegradable delivery scaffold based on poly(lactide)-graft-poly(ethylene glycol) (PLA-g-PEG) is introduced and tested in vitro. The use of a functional ring-opening polymerization initiator (containing a masked aldehyde) on an azido PEG-lactide monomer combines two known methodologies to afford functionalized PLA. The resulting copolymer features two compatible functional groups and decreased hydrophobicity due to the PEG. The functional groups are capable of performing high-yielding orthogonal postpolymerization reactions, namely strain-promoted azide-alkyne click chemistry and reductive amination. PLA-g-PEG was functionalized with a fluorescent dye (7-nitrobenzoxadiazole, NBD) and a cell internalization peptide, gH625. The resulting delivery vehicle was investigated for cell uptake with HeLa cells, showing that the gH625 conjugation exhibited enhanced cellular uptake and localization in close proximity to the nuclei. The presented methodology is a new approach toward targeted delivery