Brush-first synthesis of core-photodegradable miktoarm star polymers via ROMP: towards photoresponsive self-assemblies.

This report describes the synthesis of miktoarm brush-arm star polymers (BASPs) from branched and linear norbornene-terminated macromonomers (MMs) via the brush-first ring-opening metathesis polymerization (ROMP) method. First, a polystyrene (PS)-branch-poly(lactic acid) (PLA) MM is synthesized via a combination of atom transfer radical polymerization (ATRP), tin(II)-mediated ring opening polymerization, and copper-catalyzed azide-alkyne cycloaddition reactions. Graft-through ROMP of this MM followed by in situ cross-linking with a photo-cleavable bis-norbornene derivative provided nanoscopic BASPs with photodegradable cores and a precise 1:1 PS:PLA arm composition.

Brush-first and click: efficient synthesis of nanoparticles that degrade and release doxorubicin in response to light.

New strategies for the synthesis of multifunctional particles that respond to external stimuli and release biologically relevant agents will enable the discovery of new formulations for drug delivery. In this article, we combine two powerful methods: brush-first ring-opening metathesis polymerization and copper-catalyzed azide-alkyne cycloaddition click chemistry, for the synthesis of a novel class of brush-arm star polymers (BASPs) that simultaneously degrade and release the anticancer drug doxorubicin (DOX) in response to 365 nm light. In vitro cell viability studies were performed to study the toxicity of azide- and DOX-loaded BASPs.

"Brush-first" method for the parallel synthesis of photocleavable, nitroxide-labeled poly(ethylene glycol) star polymers.

We describe the parallel, one-pot synthesis of core-photocleavable, poly(norbornene)-co-poly(ethylene glycol) (PEG) brush-arm star polymers (BASPs) via a route that combines the "graft-through" and "arm-first" methodologies for brush polymer and star polymer synthesis, respectively. In this method, ring-opening metathesis polymerization of a norbornene-PEG macromonomer generates small living brush initiators. Transfer of various amounts of this brush initiator to vials containing a photocleavable bis-norbornene cross-linker yielded a series of water-soluble BASPs with low polydispersities and molecular weights that increased geometrically as a function of the amount of bis-norbornene added.

EPR study of spin labeled brush polymers in organic solvents.

Spin-labeled polylactide brush polymers were synthesized via ring-opening metathesis polymerization (ROMP), and nitroxide radicals were incorporated at three different locations of brush polymers: the end and the middle of the backbone, and the end of the side chains (periphery). Electron paramagnetic resonance (EPR) was used to quantitatively probe the macromolecular structure of brush polymers in dilute solutions. The peripheral spin-labels showed significantly higher mobility than the backbone labels, and in dimethylsulfoxide (DMSO), the backbone end labels were shown to be more mobile than the middle labels.

Drug-loaded, bivalent-bottle-brush polymers by graft-through ROMP.

Graft-through ring-opening metathesis polymerization (ROMP) using ruthenium N-heterocyclic carbene catalysts has enabled the synthesis of bottle-brush polymers with unprecedented ease and control. Here we report the first bivalent-brush polymers; these materials were prepared by graft-through ROMP of drug-loaded polyethylene-glycol (PEG) based macromonomers (MMs). Anticancer drugs doxorubicin (DOX) and camptothecin (CT) were attached to a norbornene-alkyne-PEG MM via a photocleavable linker.

Core-clickable PEG-branch-azide bivalent-bottle-brush polymers by ROMP: grafting-through and clicking-to.

The combination of highly efficient polymerizations with modular "click" coupling reactions has enabled the synthesis of a wide variety of novel nanoscopic structures. Here we demonstrate the facile synthesis of a new class of clickable, branched nanostructures, polyethylene glycol (PEG)-branch-azide bivalent-brush polymers, facilitated by "graft-through" ring-opening metathesis polymerization of a branched norbornene-PEG-chloride macromonomer followed by halide-azide exchange. The resulting bivalent-brush polymers possess azide groups at the core near a polynorbornene backbone with PEG chains extended into solution; the structure resembles a unimolecular micelle.