title: Codelivery of dual drugs from polymeric micelles for simultaneous targeting of both cancer cells and cancer stem cells.
abstract: OBJECTIVE
  Phenformin-loaded micelles (Phen M) were used in combination with gemcitabine-loaded micelles (Gem M) to study their combined effect against H460 human lung cancer cells and cancer stem cells (CSCs) in vitro and in vivo.
  
  
  METHODS
  Gem M and Phen M were prepared via self-assembly of a mixture of a diblock copolymer of PEG and urea-functionalized polycarbonate (PEG-PUC) and a diblock copolymer of PEG and acid-functionalized polycarbonate (PEG-PAC) through hydrogen bonding and ionic interactions. Gem M and Phen M were characterized and tested for efficacy both in vitro and in vivo against cancer cells and CSCs.
  
  
  RESULTS
  The combination of Gem M/Phen M exhibited higher cytotoxicity against CSCs and non-CSCs than Gem M and Phen M alone, and showed significant cell cycle growth arrest in vitro. The combination therapy had superior tumor suppression and apoptosis in vivo without inducing toxicity to liver and kidney.
  
  
  CONCLUSIONS
  The combination of Gem M and Phen M may be potentially used in lung cancer therapy.
authors.affiliation: Institute of Bioengineering & Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.|NUS Graduate School for Integrative Sciences & Engineering, National University of Singapore, 117456, Singapore.
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Krishnamurthy
authors.affiliation: Institute of Bioengineering & Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
authors.forename: Victor W L
authors.initials: VW
authors.lastname: Ng
authors.affiliation: Institute of Bioengineering & Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
authors.forename: Shujun
authors.initials: S
authors.lastname: Gao
authors.affiliation: Institute of Bioengineering & Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
authors.forename: Min-Han
authors.initials: MH
authors.lastname: Tan
authors.affiliation: IBM Almaden Research Center, 650 Harry Road, San Jose, CA 95120, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Hedrick
authors.affiliation: Institute of Bioengineering & Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.
authors.forename: Yi Yan
authors.initials: YY
authors.lastname: Yang
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D010629:Phenformin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D011076:Polycarboxylate Cement / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D014508:Urea / Q000031:analogs & derivatives; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D008823:Micelles; D011076:Polycarboxylate Cement; D003841:Deoxycytidine; C005506:polycarbonate; D011092:Polyethylene Glycols; D014508:Urea; D010629:Phenformin; D000093542:Gemcitabine
keywords: cancer stem cells; codelivery; gemcitabine; in vivo efficacy; lung cancer; micellar nanoparticles; phenformin