title: Enhanced anti-cancer efficacy to cancer cells by doxorubicin loaded water-soluble amino acid-modified β-cyclodextrin platinum complexes.
abstract: The effective targeted delivery of insoluble anticancer drugs to increase the intracellular drug concentration has become a focus in cancer therapy. In this system, two water-soluble amino acid-modified β-cyclodextrin (β-CD) platinum complexes were reported. They showed preferable binding ability to DNA and effective inhibition to cancer cells, and they could bind and unwind pBR322 DNA in a manner which was similar to cisplatin. Besides, our platinum complexes could effectively deliver the anticancer drug doxorubicin (Dox) into cells and had higher cell inhibition ratio, but less toxicity on the normal cells, compared with cancer cells. In this combination system, Dox was encapsulated into the hydrophobic cavities of β-CD at the optimum molar ratio of 1:1, which were validated by UV-visible (UV-vis) absorption spectroscopy, fluorescence spectroscopy and MTT experiments. Moreover, the combination system had higher cell inhibition ratio than free Dox and amino acid-modified β-CD platinum complexes, and the results of high content screening (HCS) showed that Dox-loaded amino acid-modified β-CD platinum complexes could permeate the cell membrane and enter cells, suggesting the efficient transport of Dox across the membranes with the aid of the β-CD. We expect that the amino acid-modified β-CD platinum complexes will deliver the antitumor drug Dox to enhance intracellular drug accumulation and such combination system showed great potential as an antitumor drug.
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng 475004, China; MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China.
authors.forename: Mei-Xia
authors.initials: MX
authors.lastname: Zhao
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng 475004, China.
authors.forename: Er-Zao
authors.initials: EZ
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng 475004, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China.
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Li
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cao
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China.
authors.forename: Cai-Ping
authors.initials: CP
authors.lastname: Tan
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China.
authors.forename: Liang-Nian
authors.initials: LN
authors.lastname: Ji
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China. Electronic address: cesmzw@mail.susy.edu.cn.
authors.forename: Zong-Wan
authors.initials: ZW
authors.lastname: Mao
mesh_terms: D000596:Amino Acids / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D017671:Platinum Compounds / Q000008:administration & dosage / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D004337:Drug Carriers; D017671:Platinum Compounds; D047392:beta-Cyclodextrins; D014867:Water; D004317:Doxorubicin; C031215:betadex
keywords: Combination system; Cyclodextrin; Doxorubicin; Drug delivery; Platinum complexes