Drug-Loaded, Bivalent-Bottle-Brush Polymers by Graft-through ROMP

Johnson, Jeremiah A.; Lü, Ying; Burts, Alan O.; Xia, Yan; Durrell, Alec C.; Tirrell, David A.; Grubbs, Robert H.

doi:10.1021/ma1021506

Cited by 298 publications

(289 citation statements)

References 62 publications

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“…Bottlebrush block copolymers have a lower critical micelle concentration compared with linear diblock copolymers and surfactants. A series of bottlebrush polymers and block copolymers with different exterior and interior structures has been demonstrated: bottlebrushes with hydrophilic exteriors and hollow interiors 95,124 , bottlebrushes with covalently attached drug molecules 125,126,136 , and Janustype amphiphilic bottlebrushes 128 . Bottlebrush polymers and copolymers have been shown to provide on-demand drug release 137 with the capability for targeting through molecular recognition 133 .…”

Section: Discussionmentioning

confidence: 99%

“…The drugs were attached through a light-responsive molecule, and grafting-through ROMP yielded water-soluble bottlebrushes with triggered drug release through light exposure. The cytotoxicity of all bottlebrush polymers studied increased by more than 10 times upon UV irradiation 125 . In an alternative approach, Johnson et al synthesized water-soluble, UV-responsive bottlebrush drug carriers through copper-catalyzed alkyne-azide "click to" reactions 1 .…”

Section: Non-associating Bottlebrushes For Encapsulation and Deliverymentioning

confidence: 97%

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Structure, function, self-assembly, and applications of bottlebrush copolymers

et al. 2015

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Bottlebrush polymers are a type of branched or graft polymer with polymeric side-chains attached to a linear backbone, and the unusual architecture of bottlebrushes provides a number of unique and potentially useful properties. These include a high entanglement molecular weight, enabling rapid self-assembly of bottlebrush block copolymers into large domain structures, the self-assembly of bottlebrush block copolymer micelles in a selective solvent even at very low dilutions, and the functionalization of bottlebrush side-chains for recognition, imaging, or drug 2 delivery in aqueous environments. This review article focuses on recent developments in the field of bottlebrush polymers with an emphasis on applications of bottlebrush copolymers.Bottlebrush copolymers contain two (or more) different types of polymeric side-chains. Recent work has explored the diverse properties and functions of bottlebrush polymers and copolymers in solutions, films, and melts, and applications explored include photonic materials, bottlebrush films for lithographic patterning, drug delivery, and tumor detection and imaging. We provide a brief introduction to bottlebrush synthesis and physical properties and then discuss work related to: i) bottlebrush self-assembly in melts and bulk thin films, ii) bottlebrushes for photonics and lithography, iii) bottlebrushes for small molecule encapsulation and delivery in solution, and iv) bottlebrush micelles and assemblies in solution. We briefly discuss three potential areas for future research, including developing a more quantitative model of bottlebrush self-assembly in the bulk, studying the properties of bottlebrushes at interfaces, and investigating the solution assembly of bottlebrush copolymers.

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Section: Discussionmentioning

confidence: 99%

Section: Non-associating Bottlebrushes For Encapsulation and Deliverymentioning

confidence: 97%

Structure, function, self-assembly, and applications of bottlebrush copolymers

et al. 2015

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“…Furthermore, surface-or core-functionalized star polymers and miktoarm star polymers could be prepared via arm-first crosslinking of appropriate telechelic or branched MMs. [10][11][12][13]53 ■ RESULTS AND DISCUSSION In Matyjaszewski's work, (meth)acrylate-terminated MMs, an alkyl bromide initiator, cross-linker (e.g., divinylbenzene), and copper catalyst are typically combined at the outset of polymerization. As a result, star cores are formed rapidly via a statistical combination of star+star and star+linear reactions between MM, cross-linker, and newly formed stars.…”

Section: ■ Introductionmentioning

confidence: 99%

“Brush-First” Method for the Parallel Synthesis of Photocleavable, Nitroxide-Labeled Poly(ethylene glycol) Star Polymers

et al. 2012

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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. The BASP cores were cleaved upon exposure to UV light; the extent of photo-disassembly depended on the amount of cross-linker. EPR spectroscopy of nitroxide-labeled BASPs was used to probe differences between the BASP core and surface environments. We expect that BASPs will find applications as easy-to-synthesize, stimuli-responsive core−shell nanostructures.

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“…A triggered release can be achieved by the utilization of a specific linker molecule between drug and polymer which is cleavable upon the appliance of a certain trigger. [298][299][300][301] An interesting example to realize this concept was recently described by Choi et al The investigated approach is based on a doxorubicin-PAMAM dendrimer conjugate where the hydrophilic drug is connected to the preformed dendrimer via a photo-cleavable linker. 302 As this was shown to be highly efficient for the release of doxorubicin upon irradiation, it is of great interest to extend this conception to a broad variety of polymeric carrier systems such as e.g.…”

Section: Light-sensitive Microgel-doxorubicin Conjugates: Labile Drugmentioning

confidence: 99%

Light-Sensitive Polymeric Nanoparticles Based on Photo-Cleavable Chromophores

Klinger

2013

Springer Theses

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This thesis focuses on the design, synthesis and characterization of novel photo-sensitive microgels and nanoparticles as potential materials for the loading and light-triggered release/accessibility of functional compounds. In order to realize this concept, different approaches to irradiation-dependent response mechanisms have been investigated.Novel light-cleavable divinyl functionalized monomeric crosslinkers based on o-nitrobenzyl derivatives were synthesized and used for the preparation of either PMMA or hydroxyl functionalized PHEMA microgels swellable and degradable in organic solvents. By the introduction of anionic MAA moieties into the PHEMA microgels, this concept was successfully transferred to double stimuli-responsive p(HEMA-co-MAA) hydrogel nanoparticles exhibiting a pH-dependent swelling and light-induced degradation behavior in aqueous media. This sensitivity to two orthogonal triggers is proposed to combine a pHinduced post-formation loading mechanism with a pH-and light-triggered release. In addition, a new class of enzyme-and light-sensitive PAAm microgels based on (meth-)acrylate functionalized dextrans as photo-and enzymatically degradable macromolecular crosslinkers was developed by introducing a photo-labile linker between the enzymatically degradable dextran chain and the polymerizable vinyl moieties. Here, the water solubility of the crosslinkers is assumed to enable an in situ loading approach of hydrophilic compounds.A different approach to the loading of microgels is based on photo-labile covalent microgel-drug conjugates. The first step to the realization of this concept was achieved by the development of a novel functional monomer consisting of a doxorubicin molecule covalently attached to a radically polymerizable methacrylate group via a photo-cleavable linker.Moreover, in order to enable the release of hydrophobic substances in aqueous media, hydrophobic nanoparticles consisting of a photo-resist polymer were designed to be degradable upon irradiation in water. Light-triggered conversion of the initial hydrophobic polymer into hydrophilic PMAA induced in situ particle dissolution and release of nile red.Since the introduction of a stimuli-responsive shell around a microgel is assumed to prevent leakage of embedded compounds, studies on non-stimuli-responsive shell formation around preformed microgel seed particles and the formation of microgel cores in polymeric shells were conducted to investigate potential synthetic pathways to this approach.In a last attempt, the surface of PHEMA and p(HEMA-co-MAA) microgels was functionalized with cinnamoyl groups in order to trigger the (reversible) particles interaction with each other by light-induced [2+2] cycloaddition reactions.

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Drug-Loaded, Bivalent-Bottle-Brush Polymers by Graft-through ROMP

Cited by 298 publications

References 62 publications

Structure, function, self-assembly, and applications of bottlebrush copolymers

Structure, function, self-assembly, and applications of bottlebrush copolymers

“Brush-First” Method for the Parallel Synthesis of Photocleavable, Nitroxide-Labeled Poly(ethylene glycol) Star Polymers

Light-Sensitive Polymeric Nanoparticles Based on Photo-Cleavable Chromophores

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