Thioaptamer-conjugated CD44-targeted delivery system for the treatment of breast cancer in vitro and in vivo |
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Authors: | Wei Fan Xiang Wang Baoyue Ding Haimin Cai Xudong Wang Yueqi Fan |
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Institution: | 1. Department of General Surgery, Wuhan General Hospital of Guangzhou Military Command Region, Wuhan, People’s Republic of China,;2. Department of Pharmaceutics, CPLA No. 425 Hospital, Sanya, People’s Republic of China,;3. Department of Pharmaceutics, CPLA No. 98 Hospital, Huzhou, People’s Republic of China, and;4. Department of Pharmaceutics, Jiaxing University School of Medicine, Jiaxing, People’s Republic of China;5. Department of Pharmaceutics, CPLA No. 425 Hospital, Sanya, People’s Republic of China, |
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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. |
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Keywords: | Breast cancer CD44 microRNA targeted delivery thioaptamer |
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