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

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.