Thermo-Gelling Dendronized Chitosans for Modulating Protein Activity

Abstract

Regulation of protein activity is important in their applications for biomedicine and therapeutics. Here, an approach for the regulation of protein bioactivity through molecular confinement provided by oligoethylene glycol (OEG)-based dendronized chitosan (DCS) hydrogels is reported. Structural effects on their thermoresponsiveness are investigated. The highly transparent hydrogels are formed from thermoresponsive DCSs through their thermal dehydration and exhibit an intriguing reversible sol–gel transition property when triggered at physiological temperatures. The thermo-gelling behavior and mechanical strength of these hydrogels are investigated, and possible effects from hydrophobicity of the OEG dendrons, grafting rates of the dendrons on the chitosan main chain, and solid content of polymers are examined. These DCS hydrogels are found to have lamellar morphologies and can provide characteristic hydrophobicity microenvironments formed through the crowded OEG dendrons, which show a higher level of confinement to guest proteins. This allows the DCS hydrogels remarkable activity protection capability to proteins. Furthermore, these DCS hydrogels inherit the degradability from chitosan, allowing protein release from these hydrogels through the controllable ways without impairing their activities.

Dendronization of chitosan to afford unprecedent thermoresponsiveness and tunable microconfinement

“…3A and B), where the dendron grafting ratios on DCSs were calculated by acid–base titration. 71 (2) DC XX pendanted with short lengths of OEG chains was more hydrophobic, and exhibited lower T cp and sharper phase transition with smaller hysteresis compared to the TC XX with the similar grafting ratios (Fig. 3A and C).…”

“…However, their dilute solutions turned into turbid at elevated temperature, indicating characteristic thermoresponsive behavior, and the cloud point temperatures ( T cp s) are dependent on topological structure, grafting ratio of OEG dendrons, and concentration of DCSs. 71,72 The corresponding concentrated solutions (>0.5 wt%) transformed into gels over the gelation points ( T gel ). The main results include: (1) both the T cp s and T gel s of the DCSs decreased with the increase of dendron coverage (Fig.…”

“…23,77,78 Recently, biomedical hydrogels with remarkable functions (stimuli-responsiveness, recognition, and activity regulation) have been continuously developed to modulate the migration or intermolecular association of guest molecules in a controlled manner, and have been used for switchable encapsulation of guests. 31,71,76,79…”

“…This assembly behavior of DCSs in water has been confirmed to contribute to thermally-induced aggregation and gelation of the polymers. 35,71…”

Thermoresponsive Dendronized Microgels through In Situ Cross-Linking Polymerization to Exhibit Enhanced Confinement for Solvatochromic Dyes

“…Interestingly, these crowded polymers dehydrate heterogeneously, with the peripherals collapsing first and the interior parts dehydrating at much higher temperatures. , This finding paved the way for a promising approach to form molecular envelopes surrounding the polymer backbones through thermal dehydration, ensuring tunable encapsulation and protection of guest moieties or guest molecules , and even modulation of chemical reactions through recognition or efficient reduction to form metal nanomaterial composites . Through the formation of spherical microgels or hydrogels, these dendronized polymers afford higher-level encapsulation and can protect efficiently guest proteins from denaturation or biodegradation. − Solvation differences during the thermally mediated collapse can modulate the transition of hydrophilic dendritic OEG moieties from the core of the aggregates to their periphery, providing a novel way to transfer encapsulated guests in a well-controlled fashion . More recently, we found that OEG-based dendronized macromonomers themselves exhibit characteristic thermoresponsive behavior, dependent on their overall hydrophilicity, concentration, and branching density (2-fold, 3-fold, 4-fold, and 6-fold) of dendritic OEGs .…”