Pontus Lundberg

Poly(ethylene glycol)-Based Thiol-ene Hydrogel Coatings−Curing Chemistry, Aqueous Stability, and Potential Marine Antifouling Applications

Photocured thiol-ene hydrogel coatings based on poly(ethylene glycol) (PEG) were investigated for marine antifouling purposes. By varying the PEG length, vinylic end-group, and thiol cross-linker, a library of hydrogel coatings with different structural composition was efficiently accomplished, with or without ester linkages. The thiol-methacrylate and thiol-allyl systems were evaluated with respect to curing, degradation, as well as antifouling properties. Methacrylate-based systems exhibited homopolymerization, whereas allyl-based systems reacted more selectively through thiol-ene couplings reaction. The ester-free hydrogels elucidated higher hydrolytic stability whereas longer PEG chains accelerated the degradation process. The antifouling properties were evaluated by protein adsorption with Bovine serum albumin (BSA) and bioassays with the marine bacteria, Cobetia marina, and the marine diatom, Amphora coffeaeformis; in all tests, longer PEG lengths improved the antifouling properties.

Linear dendritic polymeric amphiphiles with intrinsic biocompatibility: synthesis and characterization to fabrication of micelles and honeycomb membranes

Linear dendritic hybrid materials enable a range of architectural variations which offers novel possibilities in the tailoring of polymeric materials. In this study dendrons based on the 2,2-bis(methylol)propionic acid (bis-MPA) building block, bearing click chemistry moieties in the core and peripheral hydroxyl functionalities, have been used as macroinitiators for ring opening polymerization of e-caprolactone. A library of star branched polymers with poly(e-caprolactone) chains was initially constructed using dendrons up to 4th generation. In a second step, the popular CuAAC or thiol–ene click reaction was efficiently used to attach poly(ethylene glycol) chains of different lengths to the core. Potential applications of the resulted amphiphilic linear dendritic hybrids were investigated. Both self-assembled micelles loaded with doxorubicin anticancer drug and ordered honeycomb membranes with enhanced surface area were successfully fabricated and characterized.

pH-triggered self-assembly of biocompatible histamine-functionalized triblock copolymers

Histamine functionalized poly(allyl glycidyl ether)-b-poly(ethylene glycol)-b-poly(allyl glycidyl ether) (PAGE-PEO-PAGE) triblock copolymers represent a new class of physically cross-linked, pH-responsive hydrogels with significant potential for biomedical applications. These telechelic triblock copolymers exhibited abrupt and reversible hydrogelation above pH 7.0 due to a hudrophilic/hydrophobic transition of the histamine units to form a network of hydrophobic domains bridged by a hydrophilic PEO matrix. These hydrophobic domains displayed improved ordering upon increasing pH and self-assembled into a body centered cubic lattice at pH 8.0, while at lower concentrations formed well-defined micelles. Significantly, all materials were found to be non-toxic when evaluated on three different cell lines and suggests a range of medical and biomedical applications.

Mussel-Inspired Anchoring of Polymer Loops That Provide Superior Surface Lubrication and Antifouling Properties

We describe robustly anchored triblock copolymers that adopt loop conformations on surfaces and endow them with unprecedented lubricating and antifouling properties. The triblocks have two end blocks with catechol-anchoring groups and a looping poly(ethylene oxide) (PEO) midblock. The loops mediate strong steric repulsion between two mica surfaces. When sheared at constant speeds of ∼2.5 μm/s, the surfaces exhibit an extremely low friction coefficient of ∼0.002-0.004 without any signs of damage up to pressures of ∼2-3 MPa that are close to most biological bearing systems. Moreover, the polymer loops enhance inhibition of cell adhesion and proliferation compared to polymers in the random coil or brush conformations. These results demonstrate that strongly anchored polymer loops are effective for high lubrication and low cell adhesion and represent a promising candidate for the development of specialized high-performance biomedical coatings.

A one component methodology for the fabrication of honeycomb films from biocompatible amphiphilic block copolymer hybrids: a linear–dendritic–linear twist

The development of a facile method for the fabrication of breath figure (BF) films from hydrophobic polymers is gaining significant importance for their accessibility as templates in fields ranging from electronics and cell culturing to sensing and catalysis. By introducing polyester-based dendritic linkers, a library of micrometre sized honeycomb structures was successfully fabricated from amphiphilic linear–dendritic–linear hybrids comprising hydrophobic PCL or PLA and hydrophilic PEG blocks. From the array of produced films, the incorporation of a third generation dendritic linker was found to generate well-ordered honeycomb films in the several hundreds of micrometre range. This one component approach minimizes the number of unknown parameters and represents a fully reliable methodology for the fabrication of functional BFs from challenging and biocompatible polymers.

Histamine-functionalized copolymer micelles as a drug delivery system in 2D and 3D models of breast cancer†

Histamine functionalized block copolymers based on poly(allyl glycidyl ether)-b-poly(ethylene oxide) (PAGE-b-PEO) were prepared with different ratios of histamine and octyl or benzyl groups using UV-initiated thiol-ene click chemistry. At neutral pH, the histamine units are uncharged and hydrophobic, while in acidic environments, such as in the endosome, lysosomes, or extracellular sites of tumours, the histamine groups are positively charged and hydrophilic. pH responsible polymer drug delivery systems is a promising route to site specific delivery of drugs and offers the potential to avoid side effects of systemic treatment. Our detailed in vitro experiments of the efficacy of drug delivery and the intracellular localization characteristics of this library of NPs in 2D and 3D cultures of breast cancer revealed that the 50% histamine-modified polymer loaded with DOX exhibited rapid accumulation in the nucleus of free DOX within 2 h. Confocal studies showed enhanced mitochondrial localization and lysosomal escape when compared to controls. From these combined studies, it was shown that by accurately tuning the structure of the initial block copolymers, the resulting self-assembled NPs can be designed to exploit histamine as an endosomal escape trigger and the octyl/benzyl units give rise to a hydrophobic core resulting in highly efficacious drug delivery systems (DDS) with control over intracellular localization. Optimization and rational control of the intracellular localization of both DDS and the parent drug can give nanomedicines a substantial increase in efficacy and should be explored in future studies.

Physiologically relevant, pH-responsive PEG-based block and statistical copolymers with N,N-diisopropylamine units

In order to impart pH-responsiveness within a physiologically-relevant context to PEG-based biomaterials, a new tertiary amine containing repeat unit, N,N-diisopropyl ethanolamine glycidyl ether (DEGE), was developed and incorporated into statistical and block copolymers with ethylene oxide (EO), and allyl glycidyl ether (AGE) via anionic ring-opening polymerization. The reactivity of this novel monomeric building block in copolymerizations with EO was investigated by spectroscopy with observed reactivity ratios of rDEGE = 1.28 ± 0.14 and rEO = 0.82 ± 0.10. It was further demonstrated that DEGE containing copolymers could serve as building blocks for the formation of new pH-responsive materials with a pKa of ca. 9, which allowed macroscopic hydrogels to be prepared from symmetric triblock copolymers PDEGE5.3k-b-PEO20k-b-PDEGE5.3k. The triblock copolymers exhibited clear sol-to-gel transitions in a physiologically-relevant critical gelation range of pH 5.8-6.6 and pH-dependent viscoelastic properties. On the nanometer scale, the preparation of pH-responsive micro- or nanogels was demonstrated by crosslinking P(DEGE-co-AGE) copolymers in miniemulsion droplets stabilized by PEO-b-P(DEGE-co-AGE) diblock terpolymers. These nanoparticles exhibited a reversible pH-dependent swelling profile with a volume phase transition at physiological pH 6.5-7.5.

A robust platform for functional microgels via thiol–ene chemistry with reactive polyether-based nanoparticles

We herein report the development of crosslinked polyether particles as a reactive platform for the preparation of functional microgels. Thiol-ene crosslinking of poly(allyl glycidyl ether) in miniemulsion droplets - stabilized by a surface active, bio-compatible polyethylene glycol block copolymer - resulted in colloidal gels with a PEG corona and an inner polymeric network containing reactive allyl units. The stability of the allyl groups allows the microgels to be purified and stored before a second, subsequent thiol-ene functionalization step allows a wide variety of pH- and chemically-responsive groups to be introduced into the nanoparticles. The facile nature of this synthetic platform enables the preparation of microgel libraries that are responsive to different triggers but are characterized by the same size distribution, surface functionality, and crosslinking density. In addition, the utilization of a crosslinker containing cleavable ester groups renders the resulting hydrogel particles degradable at elevated pH or in the presence of esterase under physiological conditions.

A synthetic strategy for the preparation of sub-100 nm functional polymer particles of uniform diameter

An amphiphilic block copolymer surfactant is used to impart peripheral surface functionality to polymer nanoparticles synthesized via emulsion polymerization. Particles ranged in size from ca. 55 nm by SEM (ca. 82 nm by DLS) to just over 200 nm. Particles displaying latent functionality were readily functionalized directly after polymerization using a fluorescent dye.