title: Characterization of high-affinity peptides and their feasibility for use in nanotherapeutics targeting leukemia stem cells.
abstract: Peptides featuring the LR(S/T) motif were identified that could specifically bind to the C-type lectin-like molecule-1 (CLL1), a protein preferentially expressed on acute myeloid leukemia stem cells (LSCs). Micellar nanoparticles were covalently decorated with CLL1-targeting peptides for targeted drug delivery. The resulting peptide-coated nanoparticles were 13.5 nm in diameter and could be loaded with 5 mg of daunorubicin per 20 mg of telodendrimers. These "targeting nanomicelles" transported the drug load to the interior of cells expressing CLL1 and to LSCs isolated from clinical specimens in vitro, but did not bind to normal blood or normal hematopoietic stem cells. The presence of CLL1-targeting peptides on the surface of the nanomicelles enabled the improved binding and delivery of substantially more daunorubicin into the cells expressing CLL1 and CD34(+) leukemic cells compared with unmodified nanomicelles. In conclusion, nanomicelles coated with CLL1-targeting peptides are potentially useful for eradicating LSCs and improving leukemia therapy.
  
  
  BACKGROUND
  Micellar nanoparticles covalently decorated with targeting peptides were used for targeted drug delivery of daunorubicin to address acute myeloid leukemia stem cells.
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of California at Davis, Sacramento, California, USA.
authors.forename: Hongyong
authors.initials: H
authors.lastname: Zhang
authors.forename: Juntao
authors.initials: J
authors.lastname: Luo
authors.forename: Yuanpei
authors.initials: Y
authors.lastname: Li
authors.forename: Paul T
authors.initials: PT
authors.lastname: Henderson
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Wang
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wachsmann-Hogiu
authors.forename: Weixin
authors.initials: W
authors.lastname: Zhao
authors.forename: Kit S
authors.initials: KS
authors.lastname: Lam
authors.forename: Chong-xian
authors.initials: CX
authors.lastname: Pan
mesh_terms: D000595:Amino Acid Sequence; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003630:Daunorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D000903:Antibiotics, Antineoplastic; C470184:CLECL1 protein, human; D037181:Lectins, C-Type; D008565:Membrane Proteins; D010455:Peptides; D003630:Daunorubicin