ZIF-8-based core/shell nanocarriers for relieving multidrug resistance in cancer therapy

Abstract

An effective nanosystem for smart drug delivery requires that the drug be released in a controlled manner at expected locations. Zeolitic imidazolate framework-8 (ZIF-8) with high loading ability and pH-sensitive degradation properties is a suitable candidate for designing such nanoplatforms. However, the Zn²⁺ ions stemming from the degradation of ZIF-8 could cause toxicity, hindering its further practical application. Herein, to overcome this inherent toxicity, a highly stable, biocompatible, and pH-responsive functionalized ZIF-8 nanocarrier (ZIF-8/lysozyme@hydroxyapatite, ZIF-8/Lys@HAp) is rationally designed via the in situ biomimetic mineralization method. The function of the Lys within the structure is to bond metal ions strongly, thus increasing the rates of nucleation and growth. Importantly, because the overexpression of active efflux transporters is usually responsible for the multidrug resistance (MDR) effect, combining multiple drugs could efficiently avoid MDR compared to a one-drug-loaded platform. Thus, ZIF-8/Lys@HAp is studied as a nanocarrier to achieve efficient codelivery of doxorubicin hydrochloride (anticancer drug) and verapamil hydrochloride (P-glycoprotein inhibitor) to overcome MDR and enhance the therapeutic effect. Our constructed (DOX+VER)-ZIF-8/Lys@HAp represents a promising vehicle in targeted cancer therapy for reversing MDR with enhanced therapeutic efficacy, broadening the applications of ZIF-8 in the biomedical field.