Biomimetic targeting magnetite hollow nanostructures based on pH-responsive benzoic-imine bonds for antitumor activity

Abstract

In this study, versatile homotypic-targeting and PEGylated magnetite hollow nanostructures (MHNs) that are pH-responsive used as doxorubicin (DOX) nanocarriers are demonstrated. Cancer cell membrane (CM) and polyethylene glycol (PEG) functionalization through benzoic imine bonds endows DOX-conjugated nanocarriers with enhanced tumor accumulation and penetration, biomimetic-targeting specificity, as well as on-demand drug release, which improves their antitumor efficacy. The characteristic diffraction peaks of magnetite nanocarriers at 35° indexed as (311) plane of magnetite can be observed. Hierarchical mesoporous nanostructures with specific pore size distributions of approximately 99.9, 97.2, and 95.6%, were developed. In vitro studies revealed that drug-free nanostructures exhibited excellent biocompatibility with more than 95% cell viability. In contrast, drug-conjugated nanostructures demonstrated high therapeutic effect, pH-responsive drug release, and enhanced intracellular uptake in HepG2 cells. In vivostudies showed that the MHNC–DOX–PEG/CM formulations displayed the best antitumor efficacy, with the lowest tumor volume and weight. Furthermore, significantly large apoptotic and necrotic areas were identified in the tumor tissues from the DOX-conjugated groups, but no noticeable inflammation or hemorrhage was observed in the main organs. Therefore, these results suggest that the formulated nanostructures have great potential for cancer therapies.