pH-triggered degradation and release of doxorubicin from zeolitic imidazolate framework-8 (ZIF8) decorated with polyacrylic acid

Abstract

Zeolite imidazolate framework-8 (ZIF8) represents a class of highly porous materials with a very high surface area, large pore volume, thermal stability, and biocompatibility. In this study, ZIF8-based nanostructures demonstrated a high loading capacity for doxorubicin (62 mg Dox per g ZIF8) through the combination of π–π stacking, hydrogen bonding, and electrostatic interactions. Dox-loaded ZIF8 was subsequently decorated with polyacrylic acid (PAA) (ZIF8–Dox@PAA) that showed good dispersity, fluorescent imaging capability, and pH-responsive drug release. The stable localization and association of Dox in ZIF8@PAA were investigated by C13 nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy. The NMR chemical shifts suggest the formation of hydrogen bonding interactions and π–π stacking interactions between the imidazole ring of ZIF8 and the benzene ring of Dox that can significantly improve the storage of Dox in the ZIF8 nanostructure. Additionally, the release mechanism of ZIF8–Dox@PAA was discussed based on the detachment of the PAA layer, enhanced solubility of Dox, and destruction of ZIF8 at different pH conditions. In vitro release test of ZIF8–Dox@PAA at pH 7.4 showed the low release rate of 24.7% even after 100 h. However, ZIF8–Dox@PAA at pH 4.0 exhibited four stages of release profiles, significantly enhanced release rate of 84.7% at the final release stage after 30 h. The release kinetics of ZIF8–Dox@PAA was analyzed by the sigmoidal Hill, exponential Weibull, and two-stage BiDoseResp models. The ZIF8–Dox@PAA nanocarrier demonstrated a promising theranostic nanoplatform equipped with fluorescent bioimaging, pH-responsive controlled drug release, and high drug loading capacity.