PH-responsive nanoreservoirs based on hyaluronic acid end-capped mesoporous silica nanoparticles for targeted drug delivery

Abstract

Mesoporous silica nanoparticles (MSNs) are greatly appealing for efficient drug delivery due to their excellent drug loading capacities. However, it remains as a major challenge to realize site-specific controlled release with MSNs. This work examines a smart pH-responsive drug release system using MSNs for CD44-targeting drug delivery. Specifically, hyaluronic acid (HA) was applied as an end-capping agent to seal drug loads inside the mesoporous of MSNs through the acid labile hydrazine bonds. HA exposed on the surface of the particles can also serve as a targeting agent at the same time, enable site specific targeting toward CD-44 overexpressing cells. The system showed a good stability at physiological pHs, yet drug release could be triggered in response to changes in pH. Further studies showed that the HA-fabricated particles could achieve much enhanced cellular uptake via CD44 receptor-mediated endocytosis by Hela cells (CD44 receptor-positive), and as a result, doxorubicin-loaded MSNs exhibited significantly enhanced drug efficacy toward cancer cells overexpressing CD44 receptor (IC50 = 0.56 μg/mL), whereas the normal cells showed weakly cytotoxicity (IC50 = 1.03 μg/mL). Such a fabrication strategy may provide a new platform for preparation of high performance drug delivery systems for cancer therapy.