title: HER2-positive breast cancer targeting and treatment by a peptide-conjugated mini nanodrug.
abstract: HER2+ breast cancer is one of the most aggressive forms of breast cancer. The new polymalic acid-based mini nanodrug copolymers are synthesized and specifically characterized to inhibit growth of HER2+ breast cancer. These mini nanodrugs are highly effective and in the clinic may substitute for trastuzumab (the marketed therapeutic antibody) and antibody-targeted nanobioconjugates. Novel mini nanodrugs are designed to have slender shape and small size. HER2+ cells were recognized by the polymer-attached trastuzumab-mimetic 12-mer peptide. Synthesis of the nascent cell-transmembrane HER2/neu receptors by HER2+ cells was inhibited by antisense oligonucleotides that prevented cancer cell proliferation and significantly reduced tumor size by more than 15 times vs. untreated control or PBS-treated group. We emphasize that the shape and size of mini nanodrugs can enhance penetration of multiple bio-barriers to facilitate highly effective treatment. Replacement of trastuzumab by the mimetic peptide favors reduced production costs and technical efforts, and a negligible immune response.
authors: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
authors: Hui
authors: H
authors: Ding
authors: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
authors: Pallavi R
authors: PR
authors: Gangalum
authors: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
authors: Anna
authors: A
authors: Galstyan
authors: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
authors: Irving
authors: I
authors: Fox
authors: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
authors: Rameshwar
authors: R
authors: Patil
authors: Department of Biomedical Sciences, Research Division of Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
authors: Paul
authors: P
authors: Hubbard
authors: Department of Biomedical Sciences, Research Division of Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
authors: Ramachandran
authors: R
authors: Murali
authors: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
authors: Julia Y
authors: JY
authors: Ljubimova
authors: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States. Electronic address: eggehard.holler@cshs.org.
authors: Eggehard
authors: E
authors: Holler
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry; D010455:Peptides / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab
keywords: 8-arm starPEG; HER2+ breast cancer; Polymalic acid; Polymer nanoconjugate; Trastuzumab mimetic peptide