title: The biological characteristics of a novel camptothecin-artesunate conjugate.
abstract: A novel conjugate of camptothecin and artesunate (C-Q) was prepared and its cytotoxicity was evaluated using the MTT assay. In addition, the antitumour activity and toxicity of C-Q were investigated in mice, and interaction between transferrin (TF) and C-Q was investigated to evaluate its interaction with biological macromolecules. In the MTT assay, C-Q showed better inhibitory activity against MCF7 breast cancer cells and SMMC-7721 liver cancer cells than camptothecin or artesunate. In vivo, C-Q showed lower toxicity and better antitumour activity compared with camptothecin. Fluorescence spectroscopy showed static quenching of TF in the presence of C-Q, and thermodynamic parameters (ΔH>0 and ΔG<0) indicated that the reaction was spontaneous and endothermic. The main binding force between C-Q and TF was hydrophobic, as indicated by thermodynamic parameters (ΔH>0 and ΔS>0). Thus, synchronous fluorescence spectra showed that C-Q had no influence on the conformation of TF. Our results indicated that C-Q represents a novel potential anticancer therapeutic vector with advantages over current methods of CPT and ART administration. This novel drug delivery system allows the use of these drugs in a manner associated with few side effects for normal tissue, and which facilitates synergistic effects of anti-tumour drugs.
authors.affiliation: Key Laboratory of Forest Plant Ecology (Northeast Forestry University), Ministry of Education, 332 No. 26 Hexing Road, Harbin City, Heilongjiang Province 150040, China; College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China. Electronic address: li_qingyong@126.com.
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Li
authors.affiliation: Key Laboratory of Forest Plant Ecology (Northeast Forestry University), Ministry of Education, 332 No. 26 Hexing Road, Harbin City, Heilongjiang Province 150040, China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Forest Plant Ecology (Northeast Forestry University), Ministry of Education, 332 No. 26 Hexing Road, Harbin City, Heilongjiang Province 150040, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Forest Plant Ecology (Northeast Forestry University), Ministry of Education, 332 No. 26 Hexing Road, Harbin City, Heilongjiang Province 150040, China.
authors.forename: Bolin
authors.initials: B
authors.lastname: Lian
authors.affiliation: Key Laboratory of Forest Plant Ecology (Northeast Forestry University), Ministry of Education, 332 No. 26 Hexing Road, Harbin City, Heilongjiang Province 150040, China.
authors.forename: Qiaochu
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Forest Plant Ecology (Northeast Forestry University), Ministry of Education, 332 No. 26 Hexing Road, Harbin City, Heilongjiang Province 150040, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Yao
authors.affiliation: Key Laboratory of Forest Plant Ecology (Northeast Forestry University), Ministry of Education, 332 No. 26 Hexing Road, Harbin City, Heilongjiang Province 150040, China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D037621:Artemisinins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000077332:Artesunate; D002166:Camptothecin / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; D004365:Drugs, Chinese Herbal; D000077332:Artesunate; D002166:Camptothecin
keywords: Biological activity; Breast cancer; Camptothecin–artesunate conjugate; Fluorescence quenching; Liver cancer; Toxicity