GSH/pH dual-responsive and HA-targeting nano-carriers for effective drug delivery and controlled release

Drug delivery systems (DDS) for cancer therapy can increase the solubility of hydrophobic drugs, prolong drug half-life and reduce the side effects on normal tissues. However, poor targeting, biodegradability and biocompatibility of nanoparticles have greatly affected their widespread applications. Here, a glutathione (GSH)/pH dual-responsive, degradable and targeting DDS was developed using degradable dendritic mesoporous silica nanoparticles (DDMSNs) as carrier, doxorubicin (DOX) as antitumor drug and hyaluronic acid (HA) as targeting molecule (denoted as DDMSNs-DOX-HA). The engineered DDMSNs-DOX-HA with particle sizes ranging from 100 to 150 nm presented a superior loading capacity of DOX (283 mg g−1) due to their uniformly radial channel structure. The in vitro investigation under condition of pH (5.5) and GSH (10 mM) indicated that DDMSNs-DOX-HA performed excellent GSH/pH-triggered drug release behavior and were disintegrated visibly within 5 d. The proposed DDS (DDMSNs-DOX-HA) obviously represented a higher cytotoxicity against tumor cells (MCF-7) owing to its GSH/pH dual-triggered responsivity, and the recommended nano-carriers (DDMSNs-HA) showed lower cytotoxicity for MCF-7 cells. Furthermore, the results of flow cytometry revealed that the fabricated DDMSNs-DOX-HA possessed preeminent targeting function for MCF-7 cells (HA-receptor-positive) compared to L929 cells (HA-receptor-negative), likely suggesting the potential tumor-specific targeting ability. Therefore, we believe that the developed DDMSNs-DOX-HA have the potential as a promising DDS for tumor therapy and provide an inspired alternative to design multifunctional drug delivery nanoplatforms.