Preparation and Characterization of Paclitaxel-loaded PLGA nanoparticles coated with cationic SM5-1 single-chain antibody.
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.
Kou
Geng
G
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.
Gao
Jie
J
Wang
Hao
H
Chen
Huaiwen
H
Li
Bohua
B
Zhang
Dapeng
D
Wang
Shuhui
S
Hou
Sheng
S
Qian
Weizhu
W
Dai
Jianxin
J
Zhong
Yanqiang
Y
Guo
Yajun
Y
D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001667:Binding, Competitive; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005822:Genetic Vectors; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D018613:Microscopy, Confocal; D008957:Models, Genetic; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017239:Paclitaxel