Hierarchical Nanocarriers for Precisely Regulating the Therapeutic Process via Dual-Mode Controlled Drug Release in Target Tumor Cells.

A precisely controlled drug release is a great challenge in exploring methodologies of drug administration and fighting drug resistance for successful cancer chemotherapy. Herein, we developed a dual-mode nanocarrier to specifically deliver doxorubicin (Dox) and precisely control the drug release in target tumor cells. This hierarchical nanocarrier consisted of a gold nanorod as the heating core, biodegradable mesoporous silica as the storage chamber, and graphene quantum dot (GQD) as a drug carrier. The Arg-Gly-Asp peptides on the nanocarrier surface facilitated the specific interaction with integrin-overexpressed tumor cells and subsequent uptake via receptor-mediated endocytosis. Once exposed under the near-infrared (NIR) laser, the internalized nanocarrier rapidly heated the surrounding environment, which led to an instantaneous drug release by collapsing the π-π interaction between Dox and GQDs at high temperature and thereby intensified therapeutic efficacy. On the other hand, the silica shells underwent gradual degradation in the cellular matrix environment, along with stepwise liberation of the embedded GQD-Dox composites from the confined porous structure for the Dox release, exerting a long-term lethality to the tumor cells. By virtue of the physicochemical properties and synergistic behavior of the multiple components in this hierarchical nanocarrier, the NIR-triggered prompt release mode and the biodegradation-mediated slow release mode functioned in a precise and collaborative fashion, providing a promising way to manipulate the pharmacokinetics for precise cancer treatment.