Thioether-bridged mesoporous organosilica nanocapsules with weak acid-triggered charge reversal for drug delivery

Abstract

The drug delivery nanosystems with weak acid-triggered surface charge reversal function should be promising for efficient chemotherapy due to the prolonged blood circulation and enhanced the cellular uptake. However, there are only limited reports up to now. In this study, we fabricated a hybrid nanocapsule with a negative-to-positive charge-reversal outer layer triggered by the weak acidity in tumor microenvironment. The short branched polyethylenimine (PEI) with positive charge and weak acid-sensitive hexahydrophthalic anhydride with negative charge were successively modified on the surface of small uniform thioether-bridged hollow mesoporous silica nanospheres with multiple cavities. The modification of PEI as a linker was more favorable for charge reversal than that of aminopropyl group. The constructed hybrid nanocapsules exhibited weak acid (pH 6.0)-triggered charge reversal and drug release behaviors, thus effectively inhibiting the growth of A549 cancer cells. The surface functionalization of hybrid nanocapsules opens new opportunities for the development of silica-based hybrid nanosystems for promising drug delivery. Thioether-bridged hollow mesoporous silica nanocapsules with weak acid-triggered charge reverse and drug release are designed and constructed for efficient tumor drug delivery. • Branched PEI and hexahydrophthalic anhydride were modified on thioether-bridged mesoporous organosilica nanocapsules. • The constructed hybrid nanocapsules exhibited weak acid (pH 6.0)-triggered charged reversal and DOX release behaviors.