Bone-Targeted Mesoporous Silica Nanocarrier Anchored by Zoledronate for Cancer Bone Metastasis.

Abstract

Once bone metastasis occurs, the chances of survival and quality of life for cancer patients decrease significantly. With the development of nanomedicine, nanocarriers loading bisphosphonates have been built to prevent cancer metastasis based on their enhanced permeability and retention (EPR) effects; however, as a passive mechanism, the EPR effects cannot apply to the metastatic sites because of their lack of leaky vasculature. In this study, we fabricated 40 nm-sized mesoporous silica nanoparticles (MSNs) anchored by zoledronic acid (ZOL) for targeting bone sites and delivered the antitumor drug doxorubicin (DOX) in a spatiotemporally controlled manner. The DOX loading and release behaviors, bone-targeting ability, cellular uptake and its mechanisms, subcellular localization, cytotoxicity, and the antimigration effect of this drug delivery system (DDS) were investigated. The results indicated that MSNs-ZOL had better bone-targeting ability compared with that of the nontargeted MSNs. The maximum loading capacity of DOX into MSNs and MSNs-ZOL was about 1671 and 1547 mg/g, with a loading efficiency of 83.56 and 77.34%, respectively. DOX@MSNs-ZOL had obvious pH-sensitive DOX release behavior. DOX@MSNs-ZOL entered into cells through an ATP-dependent pathway and then localized in the lysosome to achieve effective intracellular DOX release. The antitumor results indicated that DOX@MSNs-ZOL exhibited the best cytotoxicity against A549 cells and significantly decreased cell migration in vitro. This DDS is promising for the treatment of cancer bone metastasis in the future.