Preparation and Characterization of Paclitaxel-loaded PLGA nanoparticles coated with cationic SM5-1 single-chain antibody |
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Authors: | Kou Geng Gao Jie Wang Hao Chen Huaiwen Li Bohua Zhang Dapeng Wang Shuhui Hou Sheng Qian Weizhu Dai Jianxin Zhong Yanqiang Guo Yajun |
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Institution: | International Joint Cancer Institute and College of Pharmacy, Second Military Medical University, New Library Building West 10th-11th Floor, 800 Xiang Yin Road, Shanghai 200433, People's Republic of China. |
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Abstract: | The purpose of this study was to develop paclitaxel-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles coated with cationic SM5-1 single-chain antibody (scFv) containing a polylysine (SMFv-polylys). SM5-1 scFv (SMFv) is derived from SM5-1 monoclonal antibody, which binds to a 230 kDa membrane protein specifically expressed on melanoma, hepatocellular carcinoma and breast cancer cells. SMFv-polylys was expressed in Escherichia coli and purified by cation-exchange chromatography. Purified SMFv-polylys was fixed to paclitaxel-loaded PLGA nanoparticles to form paclitaxel-loaded PLGA nanoparticles coated with SMFv-polylys (Ptx-NP-S). Ptx-NP-S was shown to retain the specific antigen-binding affinity of SMFv-polylys to SM5-1 binding protein-positive Ch-hep-3 cells. Finally, the cytotoxicity of Ptx-NP-S was evaluated by a non-radioactive cell proliferation assay. It was demonstrated that Ptx-NP-S had significantly enhanced in vitro cytotoxicity against Ch-hep-3 cells as compared with non-targeted paclitaxel-loaded PLGA nanoparticles. In conclusion, our results suggest that cationic SMFv-polylys has been successfully generated and may be used as targeted ligand for preparing cancer-targeted nanoparticles. |
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