A pH-Responsive Hydrogel Based on a Tumor-Targeting Mesoporous Silica Nanocomposite for Sustained Cancer Labeling and Therapy

A facile strategy is presented to synthesize hyaluronic acid (HA) and a fluorescein isothiocyanate (FITC)-conjugated mesoporous silica nanocomposite (MSN) with multiple functions of fluorescence, tumor-cell targeting, pH-triggered gelation, and enzyme-responsive drug release. This injectable nanocomposite is able to indicate the entire tumor location and provides a microenvironment with rich anticancer drugs in and around tumor tissue for a long time, to avoid recrudescence. In this design, the mesoporous silica serves as the drug container, the FITC serves as a fluorescent probe, and the anchored HA plays multiple roles as drug-release cap, tumor-targeting points, and responsive gel matrix. Owing to the specific affinity between the HA on MSNs and the CD44 antigen over-expressed on tumor cells, the MSNs can selectively attach to tumor cells. The nanocomposites then exploit the pH-responsive interactions (hydrogen bonds) among the HA to self-assemble in situ into a hydrogel around the tumor tissue. The resulting hydrogel gradually releases its payload (doxorubicin, anticancer drugs)-loaded MSNs upon HA degradation in the presence of hyaluronidase-1 (Hyal-1), followed by endocytosis and intracellular drug release. All these properties have distinct benefits for tumor treatment, demonstrating that this device is a promising candidate for oncotherapy applications.