title: Chemotherapy targeting by DNA capture in viral protein particles.
abstract: OBJECTIVE
  This study tests the hypothesis that DNA intercalation and electrophilic interactions can be exploited to noncovalently assemble doxorubicin in a viral protein nanoparticle designed to target and penetrate tumor cells through ligand-directed delivery. We further test whether this new paradigm of doxorubicin targeting shows therapeutic efficacy and safety in vitro and in vivo.
  
  
  METHODS
  We tested serum stability, tumor targeting and therapeutic efficacy in vitro and in vivo using biochemical, microscopy and cytotoxicity assays.
  
  
  RESULTS
  Self-assembly formed approximately 10-nm diameter serum-stable nanoparticles that can target and ablate HER2+ tumors at >10× lower dose compared with untargeted doxorubicin, while sparing the heart after intravenous delivery. The targeted nanoparticle tested here allows doxorubicin potency to remain unaltered during assembly, transport and release into target cells,while avoiding peripheral tissue damage and enabling lower, and thus safer, drug dose for tumor killing.
  
  
  CONCLUSIONS
  This nanoparticle may be an improved alternative to chemical conjugates and signal-blocking antibodies for tumor-targeted treatment.
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Hasmik
authors.initials: H
authors.lastname: Agadjanian
authors.forename: David
authors.initials: D
authors.lastname: Chu
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Hwang
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wachsmann-Hogiu
authors.forename: Altan
authors.initials: A
authors.lastname: Rentsendorj
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.forename: Vinod
authors.initials: V
authors.lastname: Valluripalli
authors.forename: Jay
authors.initials: J
authors.lastname: Lubow
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Behrooz
authors.initials: B
authors.lastname: Sharifi
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Farkas
authors.forename: Lali K
authors.initials: LK
authors.lastname: Medina-Kauwe
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004355:Drug Stability; D005260:Female; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D044967:Serum / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D004247:DNA; D004317:Doxorubicin; D018719:Erb-b2 Receptor Tyrosine Kinases; D014764:Viral Proteins