Engineered Dynamic Boronate Ester-Mediated Self-Healable Biocompatible G-Quadruplex Hydrogels for Sustained Release...

Injectable, self-healable, and biocompatible dynamic hydrogels prepared from the molecular self-assembly and reversible covalent bond formation of low-molecular-weight hydrogelators are increasing in the field of drug delivery. Herein, we report the formation of G-quadruplex hydrogels via the multicomponent self-assembly and reversible bond formation between guanosine (G) and 1-naphthaleneboronic acid in the presence of the monovalent cation K⁺. The cation-templated stacking interaction of G4 quartets and the formation of dynamic cyclic boronate esters are responsible for the construction of dynamic G-quadruplex assembly. The in situ-synthesized dynamic cyclic boronate esters are well characterized by ¹¹B nuclear magnetic resonance and Fourier transform infrared spectroscopy methods. The formation and morphology of the G-quadruplex hydrogel are well supported by several spectroscopic and microscopic techniques. The injectability and self-healing ability of the G-quadruplex hydrogel are also investigated. The in vivo cytotoxicity of the G-quadruplex hydrogel is extensively evaluated over different cell lines (HeLa, MCF-7, and HEK293) to observe the biostability and broad-spectrum biocompatibility of the hydrogel. Further, this injectable, biocompatible G-quadruplex hydrogel has been used for encapsulation and sustained release of two important vitamins (B₂ and B₁₂) over 40 h at physiological pH (7.46) and temperature (37 °C) without the influence of any external stimuli.