High drug loading polymer micelle@ZIF-8 hybrid core—shell nanoparticles through donor—receptor coordination interaction for pH/H2O2-responsive drug release

Abstract

Smart drug delivery nanocarriers with high drug loading capacity are of great importance in the treatment of diseases, and can improve therapeutic effectiveness as well as alleviate side effects in patients. In this work, a pH and H₂O₂-responsive drug delivery platform with high doxorubicin (DOX) loading capacity has been established through coordination interaction between DOX and phenylboronic acid containing block polymer. A composited drug nanocarrier is further fabricated by growing a zeolitic imidazolate framework 8 (ZIF-8) on the surface of drug-loaded polymer micelles. The study verifies that ZIF-8 shell can act as intelligent “switch” to prevent DOX leaking from core-shell nanoparticles upon H₂O₂ stimulus. However, a burst drug release is detected upon pH and H₂O₂ stimuli due to the further disassociation of ZIF-8 in acid solution. Moreover, the in vitro anti-cancer experiments demonstrate that the DOX-loaded core—shell nanoparticles provide effective treatment towards cancer cells but have negligible effect on normal cells, which results from the high concentration of H₂O₂ and low pH in the microenvironment of tumor cells.