Gold-Aptamer-Modified Metal–Organic Framework Drug Delivery Nanosystems for Combined Photothermal/Chemotherapy of Cancer
Ting Fang, Zihao Duan, Nan Wan, Xiaoxuan Zuo, Zhongwu Pan, Weiwei Zhang, Fei Ge, Lin Gui
Abstract
The poor targeting and high toxicity of chemotherapeutic drugs make them less effective against breast cancer. In this study, in accordance with their photothermal effect, the aptamer (Apt) (AS1411) and doxorubicin (DOX) were linked to zeolite imidazole salt frame8 (ZIF-8) by using gold nanorods (Au NRs). Thereby, a multifunctional targeting nanoparticle platform (DOX/Au-Apt@ZIF-8) was constructed to deliver and effectively utilize DOX and realize the antitumor effects of the multimodal combination of chemotherapy–target–photothermal therapy. This platform was responsive to both pH and near-infrared (NIR) light. In the characterization experiments, DOX/Au-Apt@ZIF-8 exhibited good dispersibility, particle size stability, and consistent spectral characteristics. The photothermal conversion efficiency was up to 53.5%. In the cell uptake and cell cycle experiments, DOX/Au-Apt@ZIF-8 effectively targeted tumor cells and blocked their growth in the S phase. Moreover, in an in vivo study, DOX/Au-Apt@ZIF-8 exerted good inhibitory effects and photothermal effects on tumors. When combined with NIR irradiation, DOX/Au-Apt@ZIF-8 inhibited tumor tissue growth by enhancing and inducing apoptosis. Importantly, histopathological analysis revealed that the nanoparticles were less toxic to other organs and had high biosafety. As such, DOX/Au-Apt@ZIF-8 fabricated in this study is expected to offer a treatment approach against breast cancer.