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A Smart Responsive Dual Aptamers-Targeted Bubble-Generating Nanosystem for Cancer Triplex Therapy and Ultrasound
Feifei Zhao1,2,3, Jie Zhou1,2,3, Xiangjie Su1,2,3
1School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
Abstract:
The absence of targeted, single treatment methods produces low therapeutic value for treating cancers. To increase the accumulation of drugs in tumors and improve the treatment effectiveness, near-infrared 808 nm photothermal responsive dual aptamers-targeted docetaxel (DTX)-containing nanoparticles is proposed. In this system, DTX and NH4 HCO3 are loaded in thermosensitive liposomes. The surface of liposomes is coated with gold nanoshells and connected with sulfydryl (SH) modified AS1411 and S2.2 aptamers. The nanosystem has good biocompatibility and uniform size (diameter about 200 nm). The drug is rapidly released, reaching a maximum amount (84%) at 4 h under 808 nm laser irradiation. The experiments conducted in vitro and in vivo demonstrate the nanosystem can synergistically inhibit tumor growth by combination of chemotherapy, photothermal therapy, and biological therapy. Dual ligand functionalization significantly increases cellular uptake on breast cancer cell line (MCF-7) cells and achieves ultrasound imaging (USI) at tumor site. The results indicate that this drug delivery system is a promising theranostic agent involving light-thermal response at tumor sites, dual ligand targeted triplex therapy, and USI.