Redox/pH-dual responsive functional hollow silica nanoparticles for hyaluronic acid-guided drug delivery

Stimuli-responsive nanocarriers have been studied for controlling release kinetics while minimizing the undesired leakage of loaded molecules. Hollow mesoporous silica nanoparticles (HMSNs) have been used as carriers because of their biocompatibility, porosity, high surface area, and ease of chemical modification. Moreover, introducing targeting moieties onto the HMSNs enables targeted delivery to designated sites. Here, we designed dual-responsive HMSNs capped with various molecular weights of hyaluronic acid (HA) to control the drug loading quantity and enhance the targeting efficiency. The dual-responsive HMSNs were synthesized via sequential surface grafting processes, which include thiol groups, amine groups, and capping agents (denoted as HMSN-SH, HMSN-SS-NH2, and HMSN-SS-HA, respectively). The modified HMSNs were further functionalized with HA to increase the cancer-targeting efficiency for CD44-rich cancer cells. This functionalized HMSN showed 1.2–2.3 times increased drug release efficiency under redox/pH-dual stimuli compared to each stimulus. As a result, the HMSNs were internalized by cancer cells rather than normal cells; consequently, more drugs were delivered to cancer cells. We suggest that the proposed HMSN-SS-HA would be a suitable carrier for enhancing drug delivery efficiency with targeting/stimuli-responsive functionalities.