title: Codelivery of salinomycin and chloroquine by liposomes enables synergistic antitumor activity in vitro.
abstract: To improve the suboptimal therapeutic efficacy of salinomycin (SAL) toward liver cancer cells using chloroquine (CQ) combination by the liposomes co-delivering SAL and CQ (SCNL).
  
  
  
  The synergy of these two drugs was evaluated in liver cancer cells (HepG2) and liver cancer stem cells (LCSCs) by median-effect analysis. SCNL with optimized ratio were developed. The cytotoxic effect and basal autophagy flux (measure of autophagic degradation activity) of various formulations were evaluated.
  
  
  
  CQ could significantly increase the cytotoxic effect of SAL in HepG2 cells, but not in HepG2-LCSCs, due to the greater basal autophagy flux in HepG2 cells. This combination therapy is promising for liver cancer treatment by eradicating liver cancer cells and LCSCs.
authors.affiliation: Department of Pharmaceutical Sciences, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Pharmaceutical Sciences, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Siyue
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Sciences, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Gong
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: Department of Pharmaceutical Sciences, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pharmaceutical Sciences, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zou
authors.affiliation: Department of Pharmaceutical Sciences, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Pharmaceutical Sciences, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Sciences, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Pharmacy, East Hospital of Hepatobiliary Surgery, 225 Changhai Road, Shanghai 200433, China.
authors.forename: Xinxia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, East Hospital of Hepatobiliary Surgery, 225 Changhai Road, Shanghai 200433, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, East Hospital of Hepatobiliary Surgery, 225 Changhai Road, Shanghai 200433, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhang
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Bohua
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.|International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutical Sciences, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Yanqiang
authors.initials: Y
authors.lastname: Zhong
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002738:Chloroquine / Q000008:administration & dosage* / Q000494:pharmacology; D004357:Drug Synergism; D056945:Hep G2 Cells; D006801:Humans; D008081:Liposomes; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D011714:Pyrans / Q000008:administration & dosage* / Q000494:pharmacology; D000095662:Polyether Polyketides
chemical_list: D000890:Anti-Infective Agents; D002738:Chloroquine; D008081:Liposomes; D011714:Pyrans; C010327:salinomycin; D000095662:Polyether Polyketides
keywords: autophagy; cancer stem cells; chloroquine; combined therapy; liposomes; liver cancer; salinomycin