title: Co-delivery of doxorubicin and PEGylated C16-ceramide by nanoliposomes for enhanced therapy against multidrug resistance.
abstract: OBJECTIVE
  To develop novel nanoliposomes (Lip-ADR-Cer) codelivering doxorubicin (ADR) and PEGylated C16 ceramide (PEG-ceramide C16) to overcome multidrug resistance.
  
  
  METHODS
  The antitumor activity and mechanism of Lip-ADR-Cer were evaluated.
  
  
  CONCLUSIONS
  The IC50 of Lip-ADR-Cer after 48-h treatment with the MCF-7/ADR and HL-60/ADR cancer cells, both being ADR resistant, was 2.2- and 1.4-fold effective respectively versus the general nanoliposomes with no PEG-ceramide C16 (Lip-ADR). The antitumor assay in mice bearing MCF-7/ADR or HL-60/ADR xenograft tumors confirmed the superior antitumor activity of Lip-ADR-Cer over Lip-ADR. We found that the improved therapeutic effect of Lip-ADR-Cer may be attributed to both of the cytotoxic effect of PEG-ceramide C16 and glucosylceramide synthase overexpression in multidrug resistance cells.
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Su
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.|College of Pharmacy, Liaocheng University, 1 Hu'nan Road, Liaocheng, Shandong 25200, PR China.|Centre for Stem Cell & Regenerative Medicine, Liaocheng People's Hospital, 67 Dongchang West Road, Liaocheng, Shangdong 252000, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Song
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Niu
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Kaixuan
authors.initials: K
authors.lastname: Yang
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.|College of Pharmacy, Liaocheng University, 1 Hu'nan Road, Liaocheng, Shandong 25200, PR China.
authors.forename: Geng
authors.initials: G
authors.lastname: Kou
authors.affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Wang
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Huaiwen
authors.initials: H
authors.lastname: Chen
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.|College of Pharmacy, Liaocheng University, 1 Hu'nan Road, Liaocheng, Shandong 25200, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: College of Pharmacy, Liaocheng University, 1 Hu'nan Road, Liaocheng, Shandong 25200, PR China.
authors.forename: Shangjing
authors.initials: S
authors.lastname: Guo
authors.affiliation: College of Pharmacy, Liaocheng University, 1 Hu'nan Road, Liaocheng, Shandong 25200, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.|College of Pharmacy, Liaocheng University, 1 Hu'nan Road, Liaocheng, Shandong 25200, PR China.
authors.forename: Bohua
authors.initials: B
authors.lastname: Li
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.|Department of Chemical & Biomolecular Engineering, National University of Singapore, Block E5, 02-11, 4 Engineering Drive 4, Singapore 117576, Singapore.|Suzhou NanoStar Biopharm Inc Ltd, BioBay, Bld B2, Unit 604, 218 Xing-Hu Street, Suzhou Industrial Park, Suzhou 215123, China.
authors.forename: Si-Shen
authors.initials: SS
authors.lastname: Feng
authors.affiliation: Department of Hepatobiliary Surgery, Hubei Province Tumor Hospital, Wuhan, Hubei 430079, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Yin
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.|College of Pharmacy, Liaocheng University, 1 Hu'nan Road, Liaocheng, Shandong 25200, PR China.|Department of Pharmaceutical Sciences, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002518:Ceramides / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D005964:Glucosyltransferases / Q000235:genetics; D006801:Humans; D008081:Liposomes; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D002518:Ceramides; D004338:Drug Combinations; D008081:Liposomes; D011092:Polyethylene Glycols; C097760:N-palmitoylsphingosine; D004317:Doxorubicin; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase
keywords: cancer nanotechnology; glucosylceramide synthase; molecular biomaterials; multidrug resistance; nanomedicine; pharmaceutical nanotechnology