Dendrimer-like mesoporous silica nanospheres with suitable surface functionality to combat the multidrug resistance

Abstract

Multidrug resistance (MDR), as a major obstacle in cancer therapy, has resulted in over 90% of cancer chemotherapeutic failure. Mesoporous silica nanospheres (MSNs) have been demonstrated to be tuned with large pore sizes, mediating the MDR-reversal effects. However, the study that surface functionality of the large pore sized-MSNs affects the MDR-overcoming effects hasn’t been extensively studied. In this study, we developed a new dendrimer-like MSNs delivery system based on a rational synthesis strategy and further modified MSNs with various surface functionalities to evaluate their roles in overcoming cancer MDR. Our results showed that the small particle sized-MSNs could be fabricated with dendrimer-like internal structure, resulting in the large pore size of 9 nm. Surface functionality of MSNs, especially hydroxylation and carboxylation, largely improved the intra-nuclear delivery and therapeutic efficiency of DOX for MCF7/ADR cells, which was not up to inhibiting P-gp expression but significantly increasing the intracellular drug accumulation of over 90% even under the strong drug efflux. This study indicates that surface functionality design strategy may display the potential of the large pore sized-MSNs as the efficient chemotherapeutic carriers to combat MDR.