Thioaptamer-conjugated CD44-targeted delivery system for the treatment of breast cancer in vitro and in vivo

Abstract

The high transfection efficiency and enhanced therapeutic effect of drug delivery systems developed in recent years imply that ligand-decorated nanocarriers are potentially targeted vectors for breast cancer treatment. Thioaptamer (TA)-modified nanoparticles (NPs) designed in this study mainly consisted of ligand TA and dendritic polyamidoamine (PAMAM). Knowing that TA can bind to CD44-receptors in breast cancer, this study was intended to validate the safety and feasibility of systemic miRNA delivery to breast cancer cells by TA-PEG-PAMAM/miRNA (polyethylene glycol – PEG), testify its tumor targeting efficiency in vitro, and observe its biodistribution when it was administered systemically to a xenograft mouse model of breast cancer. The in vivo and ex vivo imaging results in human breast cancer tumor-bearing mice showed that TA-modification was able to enhance the accumulation of NPs in the breast cancer tumor. Our data showed that TA-NPs did not induce functional impairment to normal tissues and vital organs. TA-NPs may prove to be a safe and effective miRNA deliver system for breast cancer treatment, and could be widely used in pre-clinical and eventually clinical arenas of breast cancer treatment.

• Breast cancer
• CD44
• microRNA
• targeted delivery
• thioaptamer

Declaration of interest

This research work was supported by the funds provided by the National Natural Science Foundation of China (No. 81402190, 81201809); Hainan Provincial Natural Science Foundation (No. 814392); the Key Scientific and Technological Project of Hainan (No. ZDXM20110036); China Postdoctoral Science Foundation (No. 2014M552711); Sanya Medical Science and Technology Innovation Project (No. YW1311); Zhejiang Provincial Natural Science Foundation of China (No. LQ12H30005); Jiaxing Science and Technology Projects (No.2012AY1075-3); CPLA Adolescent Medicine and Technology Projects (No.13QNP045; 13QNP057); and the Science and Technology Projects of Nanjing Military Command Region (No.12Z03)