Doxorubicin loaded silica nanorattles actively seek tumors with improved anti-tumor effects |
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Authors: | Gao Fuping Li Linlin Liu Tianlong Hao Nanjing Liu Huiyu Tan Longfei Li Hongbo Huang Xinglu Peng Bo Yan Chuanmiao Yang Liuqing Wu Xiaoli Chen Dong Tang Fangqiong |
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Affiliation: | Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, China. |
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Abstract: | Silica nanorattles (SNs) have proven to be promising vehicles for drug delivery. In order to further enhance efficacy and minimize adverse effects, active targeted delivery to tumors is necessary. In this work, SNs modified with a tumor specific targeting ligand, folic acid (FA), was used as carrier of doxorubicin (DOX) (DOX-FA-SNs). Drug loading, cytotoxicity and cellular uptake of DOX-FA-SNs in vitro in human cervical carcinoma cells (HeLa cells) were evaluated. DOX-FA-SNs showed a higher cytotoxicity in human cervical carcinoma cells (HeLa cells) than DOX loaded carboxyl (-COOH) and poly(ethylene glycol) (PEG) modified SNs (DOX-COOH-SNs and DOX-PEG-SNs, respectively). However, DOX-FA-SNs showed lower cytotoxicity in folate receptor negative normal mouse fibroblast cells (L929 cells) compared with free DOX. In vivo tumor-targeted fluorescence imaging indicated specific tumor targeting and uptake of FA-SNs in nude mice bearing subcutaneous HeLa cell-derived xenograft tumors. In vivo anti-tumor experiments demonstrated that DOX-FA-SNs (10 mg kg(-1) of DOX) significantly regressed the tumor growth and reduced toxicity compared with free DOX. These results have great significance in developing and optimizing SNs as effective intracellular delivery and specific tumor targeting vehicles. |
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