Carbon Dots Embedded Hybrid Microgel with Phenylboronic Acid as Monomer for Fluorescent Glucose Sensing and Glucose-Triggered Insulin Release at Physiological pH

Abstract

A multifunctional and biocompatible hybrid microgel (poly(VPBA-AAm)-CD) using N, S-doped carbon dots (CDs) and ethylene glycol dimethacrylate (EGDMA) as cross-linking agents, and 4-vinylbenzene boronic acid (VPBA) and acrylamide (AAm) as monomers, was designed in this work. This microgel can be easily prepared by a simple one-pot radical dispersion polymerization of the reactants using a rationally designed hydrogen-bonded complex method. The hybrid microgels were spherical particles with a smooth surface and an average particle size of 234 ± 8 nm. The poly(VPBA-AAm)-CD microgel displayed the glucose-responsive swelling within a clinically concerned range at a physiological pH and could realize the controllable release of insulin. In addition, the release rate of insulin in the hybrid microgel (poly(VPBA-AAm)-CD) could be triggered by glucose concentrations in the solution, and the increasing glucose concentrations can accelerate the insulin release. Further in vitro cytotoxicity studies showed that the microgel had good biocompatibility and no obvious toxicity to the cells. These indicate that the prepared microgel (poly(VPBA-AAm)-CD) may supply a new pattern for the self-regulating therapy of insulin deficiency in diabetes.

Keywords: diabetes; drug delivery; hybrid microgel; insulin.

Figure 1

SEM (a,b), TEM (c), X-ray energy spectra (d) and elemental distribution (e–k) of poly(VPBA-AAm)-CD. The inset in b is the particle size distribution of poly(VPBA-AAm)-CD hybrid microgel.

Figure 2

(a) FT-IR spectra of free CDs, poly(VPBA-AAm) microgel and poly(VPBA-AAm)-CD hybrid microgel; and (b) TGA curves of poly(VPBA-AAm) and poly(VPBA-AAm)-CD microgels.

Figure 3

(a) Fluorescence spectra of poly(VPBA-AAm)-CD: the insets are the photographs of poly(VPBA-AAm)-CD and poly(VPBA-AAm) under natural light (a′,b′) and UV light at 365 nm (c′,d′). (b) Typical fluorescence spectra of free CDs, poly(VPBA-AAm) microgel and poly(VPBA-AAm)-CDs hybrid microgel, respectively (λ_ex= 310 nm, 20 °C).

Figure 4

Influence of pH on the fluorescence intensity (a) and fluorescence emission spectrum (b) of poly(VPBA-AAm)-CD.

Figure 5

(a) Average Rh values (scattering angle θ = 90°) of poly(VPBA-AAm) and poly(VPBA-AAm)-CD at different glucose concentrations (PBS, pH = 7.4). (b) Size distribution of poly(VPB-AAm)-CD in PBS (pH = 7.4) with glucose concentrations of 0, 10 and 30 mM, respectively.

Figure 6

(a) Fluorescence spectra and (b) the variation of the fluorescence of poly(VPBA-AAm)-CD versus glucose concentration. The inset is the linear fitting plot of (F₀ − F)/F₀ versus glucose concentration (C_{poly(VPBA-AAm)-CD} = 1.75 mg/mL, PBS, pH = 7.4, λex = 310 nm).

Figure 7

Insulin release profiles from hybrid microgels at different glucose concentrations (0 mM, 5 mM, 10 mM and 20 mM, 37 °C, pH = 7.4).

Figure 8

Viability of HL-7702 cells incubated with different concentrations of poly(VPBA-AAm)-CD for 24 h and 48 h by MTT assay. * p < 0.05 compared with the control group at 24 h, # p < 0.05 compared with the control group at 48 h, “ns” means no significance.

Figure 9

Influence of metal ions (a), Fe³⁺ (b) and glucose (c) addition in that order on the fluorescence intensity of poly(VPBA-AAm)-CD. Cpoly(VPBA-AAm)-CD = 0.26 mg/mL in pH 7.4 PBS, Cmetal ions = 3.0 mM, Cglucose = 10 mM, Cascorbic acid = 7.0 mM, λem = 375 nm, λex = 310 nm.