Self-assembly and chemo-ligation strategies for polymeric multi-responsive microgels.

摘要

Microgels are sub-micron to micron-size polymeric particles swollen by a good solvent, sometimes also called hydrogel microparticles or microspheres if swollen in water. In contrast to the behavior of hard spheres, microgels behave more like soft spheres due to both steric repulsion of dangling chains tethered on their rough surface and electrostatic repulsion of charges, which could be compressed by imposing high concentration of microgels (osmotic deswelling) or higher ionic strength (compression of electric double layers). Among all microgels investigated nowadays, poly(N-alkylacrylamide), especially poly(N-isopropylacrylamide) (pNIPAm), microgels are one of the most extensively studied microgel particles due to their volume phase transition (VPT) at lower critical solution temperature (LCST). By incorporation of pH-responsive monomer, such as acrylic acid (AAc), copolymeric pNIPAm-AAc microgels further demonstrate multi-responsivity to temperature, pH, and ionic strength. A temperature-programmed polymerization protocol is proposed for the synthesis of large pNIPAm-AAc microgel particles with a hydrodynamic diameter of 2∼5 microm. To observe the phase behavior of pNIPAm-AAc microgel dispersions, pNIPAm-AAc dispersion at various pH values and concentrations was allowed to age and undergo phase transition in closed system. Immediately after preparation of concentrated pNIPAm-AAc dispersions in closed system, the average hydrodynamic diameter is smaller than the unperturbed diameter due to osmotic deswelling effect. During the aging process, pNIPAm-AAc microgel particles swell while their dynamics slow down. (Sometimes the particle size in aged dispersions is even larger than the unperturbed size!) If the effective volume fraction of pNIPAm-AAc microgel particles reaches a critical value (∼40 %), the local and global crystallization of particles are observed. If the effective volume fraction of pNIPAm-AAc dispersions is beyond packing limit (∼0.74), the compressed particles are observed in the crystalline and/or glassy phase, indicating the softness of pNIPAm-AAc microgels. The formation of crystalline phase should follow a nonergodic path in which microgel particles swell to the extent that they build up weak attractive interaction to allow them to associate while maintaining the opportunity of rearrangement to minimize local Gibbs free energy. The age-dependent thermostability of pNIPAm-AAc microgel dispersions suggests strong attractive interactions evolve between particles during crystallization. The attractive interactions are probably due to the multiple hydrogen bonding between amide and/or carboxylic acid groups on the dangling chains tethered on rough surfaces of pNIPAm-AAc microgel particles.;Finally, to introduce multiple biological "handle"s on the microgel particles for biomedical applications, the Cu(I)-catalyzed azide-terminal alkyne 1,3-dipolar cycloaddition, also called Sharpless-Meldal "click" reaction, is used to functionalize pNIPAm-AAc microgel particles. Glycidyl methacrylate (GMA) and propargyl acrylate (PA) are used to copolymerize with NIPAm and AAc to form multi-responsive microgels with "clickable" azido and acetylene groups respectively. "Clickable" fluorescent dyes are used to demonstrate the clickability of those microgels and epifluorescence microscopy is used to imaging the fluorescent particles after click reactions. Similarly, multi-functional thin films made of those clickable microgels could be fabricated via centrifugal deposition.