Fabrication of stimuli-responsive nanogels for protein encapsulation and traceless release without introducing organic solvents, surfactants, or small-molecule cross-linkers

Abstract

Stimuli-responsive nanogels were fabricated by reaction of proteins and polymers without using small-organic-molecules. Once the nanogels dissociated, the proteins were released with functional groups, secondary structures, and activities maintained.

Stimuli-responsive polypeptide nanogels for trypsin inhibition

“…In this case, loading of 1 and 0.75 mg/mL 125 I-radiolabeled BSA resulted in average loading capacities of 11.1% (11.1 µg/mL) and 14.8% (11.1 µg/mL). As was observed in other works, a high loading efficiency of 35.9% (18 µg/mL) was found when N α -Lys-NG was incubated with 0.5 mg/mL 125 I-radiolabeled BSA [31,34]. Interestingly, our results show that the amount of adsorbed 125 I-radiolabeled BSA increased with the decrease of initial concentration of the 125 Iradiolabeled BSA.…”

“…125 I-radiolabeled BSA was loaded onto PHEG-Tyr nanogel at pH 4.7 and 25 °C as PHEG-Tyr nanogel exhibits the most swollen state and a negative charge under these conditions (Figure 2). The uptake of BSA was found to be more efficient at or below the isoelectric point of BSA (pI 4.7) and, thus, BSA adsorption is driven by electrostatic and hydrophobic interactions [30,31]. PHEG-Tyr nanogel was incubated with three different 125 I-radiolabeled BSA concentrations (1, 0.75, and 0.5 mg/mL), and the loading efficiency was found to be low, that is, 2.1% (21 µg/mL), 1.9% (15 µg/mL), and 3.3% (17 µg/mL), respectively.…”

“…After the loading and release procedure was optimized for BSA, PHEG-Tyr and N α -Lys-NG nanogels were incubated with three different concentrations of 125 I-radiolabeled AAT (1, 0.75, and 0.5 mg/mL) to investigate their loading capacity and release profiles. Due to the fact that AAT has a pI in the range of 4.2-4.9, AAT was loaded at pH 4.7 as it was optimized with BSA to ensure efficient adsorption of AAT [31,32]. PHEG-Tyr nanogel again exhibited low adsorption of 125 I-radiolabeled AAT (ca.…”

Redox-responsive nanogels for drug-delivery: thiol–maleimide and thiol–disulfide exchange chemistry as orthogonal tools for fabrication and degradation

“…[28][29][30][31][32][33][34][35][36][37][38] Common degradable linkages employed are acetals, 39 imines, 40 hydrazones, 41 dithioketals, 42 and disulfide bonds. [43][44][45][46][47][48][49][50][51] In recent years, redox-responsive disulfide bonds have been used for crosslinking nanogels because of their enhanced degradation inside cancer cells due to the high intracellular GSH concentration in the cytosol. [52][53][54][55] Reactions with high efficiency are utilized to ensure the rapid crosslinking of polymeric nanogel precursors to obtain stimuli-responsive nanogels.…”

“…28–38 Common degradable linkages employed are acetals, 39 imines, 40 hydrazones, 41 dithioketals, 42 and disulfide bonds. 43–51 In recent years, redox-responsive disulfide bonds have been used for crosslinking nanogels because of their enhanced degradation inside cancer cells due to the high intracellular GSH concentration in the cytosol. 52–55…”