am7b12251_si_001.pdf (2.01 MB)
Hierarchical Nanocarriers for Precisely Regulating the Therapeutic Process via Dual-Mode Controlled Drug Release in Target Tumor Cells
journal contribution
posted on 2017-10-04, 00:00 authored by Fenfen Zheng, Penghui Zhang, Yu Xi, Xueqin Chen, Zhimei He, Tiantian Meng, Jingjia Chen, Lingling Li, Jun-Jie ZhuA 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.