Thermo- and pH-Responsive, Coacervate-Forming Hyperbranched Poly(β-amino ester)s for Selective Cell Binding

Abstract

We report a new type of thermo- and pH-responsive, coacervate-forming highly degradable polymer-hyperbranched poly(β-amino esters) (HPAEs) and its selective cell binding behaviors. The HPAEs were synthesized from 5-amino-1-pentanol (S5) and trimethylolpropane ethoxylate triacrylate (TMPETA) via an A2+B3 type Michael addition. The existence of multiple hydrogen bond pairs as well as tertiary amines makes the S5-TMPETA polymers manifest temperature- and pH-dependent phase transition. By varying the length of the ethylene glycol (EG) spacers in the TMPETA, polymer molecular weight, concentration, and pH value, the phase transition of the S5-TMPETA can be easily tuned in aqueous and buffer solutions, as evidenced by UV-vis spectroscopy and DLS measurements. Especially, the S5-TMPETA prepared from S5 and trimethylolpropane ethoxylate triacrylate 692 (S5-TMPETA692) shows a lower critical solution temperature (LCST) around 33 °C, above which the S5-TMPTEA can form coacervate particles able to encapsulate functional molecules effectively. Importantly, when incubation with HeLa cells, the S5-TMPTETA692 exhibits a temperature- and pH-responsive selective cell binding behaviors. In addition, the S5-TMPETA are highly hydrolyzable and elicit negligible cytotoxicity. This new type of "smart" polymer should find use in a variety of biomedical applications.

Soluble Hyperbranched Porous Organic Polymers

“…They exhibit versatile features such as low viscosity, good solubility, high thermal stability, and multi‐functionality . More importantly, owing to the highly branched structure, they possess a globular void‐containing structure and open conformations which offers a broad number of possible applications . The internal cavities in HBPs are entirely different to the porosity in traditional porous organic polymers (POPs) with the former being derived from the open conformation, whereas the pores in POPs are largely formed by the rigid crosslinks which prevent the polymer from collapsing.…”

Backbone‐Based LCST‐Type Hyperbranched Poly(oligo(ethylene glycol)) with CO2‐Reversible Iminoboronate Linkers

“…[6][7][8][9] Adjustment and control of the phase transition temperature of LCST-type polymers are essential for their applications. [1][2][3][4][5] For this purpose, controlled copolymerization of OEG-based acrylic esters with other stimuli-responsive monomers and various block, graft, or hyperbranched polymers of poly(ethylene glycol) have been carried out to tune their thermo-responsive behaviors. [10][11][12] Obviously, hyperbranched poly(ethylene glycol) (hPEGs) have several superiorities contrasted to the linear polyethers for use in controlled delivery system due to their globule shapes with abundant terminal functional groups and programmable internal cavities available to encapsulate guest molecules.…”

“…In recent years, water‐soluble polymers exhibiting a soluble–insoluble phase transition at the lower critical solution temperature (LCST) in water have been actively studied for their potential use in controlled drug delivery, biomedical soft materials, etc . Perhaps the ethylene glycol‐based polymers, such as poly(ethylene glycol) (PEG) or oligo(ethylene glycol) (OEG) functionalized polymers, are the most promising thermo‐responsive polymers due to their outstanding biocompatibility .…”

“…In recent years, water-soluble polymers exhibiting a solubleinsoluble phase transition at the lower critical solution temperature (LCST) in water have been actively studied for their potential use in controlled drug delivery, biomedical soft materials, etc. [1][2][3][4][5] Perhaps the ethylene glycol-based polymers, such as poly(ethylene glycol) (PEG) or oligo(ethylene glycol) (OEG) functionalized polymers, are the most promising CO 2 , [14] etc., especially in facing of the complex and everchanging environment. In our previous work, we designed a backbone-based thermo-responsive polymer of hyperbranched poly(oligo(ethylene glycol)) (HBPOEG) with CO 2 -protonable tertiary amines as branched points.…”

LCST‐Type Hyperbranched Poly(oligo(ethylene glycol) with Thermo‐ and CO2‐Responsive Backbone

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Poly(ethylene glycol) (PEG), a wellexplored biocompatible polymer, has a characteristic phase transition when heated above a certain temperature. [24][25][26][27] Due to its outstanding biocompatibility, PEG has been incorporated into polymers to form novel thermoresponsive materials, which proves their value in biomedical applications, taking drug delivery carriers as an example. Such thermoresponsive PEG-based polymers can be prepared in a designed manner via controlled polymerization with oligo(ethylene glycol) (OEG)-based acrylic ester as the comonomer.

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