NIR-responsive sandwich drug loading system for tumor targeting and multiple combined treatment

A novel drug loading system, Au@Si-NN-Si@SiO₂, is constructed by a layer-by-layer assembly approach. The core Au nanorods serve as the matrix for a near-infrared light (NIR) responsive photothermal feature. Meanwhile, the assembly's middle shell is composed of azobenzene linked silica, which produces free radicals by breaking -NN- bonds at a high temperature brought about by a NIR irradiation-caused photothermal effect, which further triggers the loaded drug release. The outer shell is formed of SiO₂ in order to prevent leakage of drug in the middle layer. The fully drug loaded nanocarriers, Au@Si-NN-Si@SiO₂-Dox, exhibit an excellent photothermal effect (43%) at a concentration of 170 μg mL^-1 under 808 nm NIR laser at 2.3 W cm^-2. The antitumor performance of Au@Si-NN-Si@SiO₂-Dox was investigated using human colon cancer cells (HCT116) as a model. By combining NIR-triggered drug release, free radical generation and the photothermal effect, the proposed Au@Si-NN-Si@SiO₂-Dox exhibits improved antitumor efficiency. By using a dosage of 170 μg mL^-1, a cell viability of 17.56% is achieved for HCT116 (5 × 10³-1 × 10⁴ cells per well) with 10 min of NIR laser irradiation (808 nm, 2.3 W cm^-2). All the results demonstrate that Au@Si-NN-Si@SiO₂-Dox exhibits wonderful dosage-dependent antitumor performance and has great potential as a therapeutic agent for tumors or even for use in the clinic.