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Dual-Ligand Modified Polymer-Lipid Hybrid Nanoparticles for Docetaxel Targeting Delivery to Her2/neu Overexpressed Human Breast Cancer Cells.

Abstract
In this study, a dual-ligand polymer-lipid hybrid nanoparticle drug delivery vehicle comprised of an anti-HER2/neu peptide (AHNP) mimic with a modified HIV-1 Tat (mTAT) was established for the targeted treatment of Her2/neu-overexpressing cells. The resultant dual-ligand hybrid nanoparticles (NPs) consisted of a poly(lactide-co-glycolide) core, a near 90% surface coverage of the lipid monolayer, and a 5.7 nm hydrated polyethylene glycol shell. Ligand density optimization study revealed that cellular uptake efficiency of the hybrid NPs could be manipulated by controlling the surface-ligand densities. Furthermore, the cell uptake kinetics and mechanism studies showed that the dual-ligand modifications of hybrid NPs altered the cellular uptake pathway from caveolae-mediated endocytosis (CvME) to the multiple endocytic pathways, which would significantly enhance the NP internalization. Upon the systemic investigation of the cellular uptake behavior of dual-ligand hybrid NPs, docetaxel (DTX), a hydrophobic anticancer drug, was successfully encapsulated into dual-ligand hybrid NPs with high drug loading for Her2/neu-overexpressing SK-BR-3 breast cancer cell treatment. The DTX-loaded dual-ligand hybrid NPs showed a decreased burst release and a more gradual sustained drug release property. Because of the synergistic effect of dual-ligand modification, DTX-loaded dual-ligand hybrid NPs exerted substantially better therapeutic potency against SK-BR-3 cancer cells than other NP formulations and free DTX drugs. These results demonstrate that the dual-ligand hybrid NPs could be a promising vehicle for targeted drug delivery to treat breast cancer.
AuthorsZhe Yang, Wenxin Tang, Xingen Luo, Xiaofang Zhang, Chao Zhang, Hao Li, Di Gao, Huiyan Luo, Qing Jiang, Jie Liu
JournalJournal of biomedical nanotechnology (J Biomed Nanotechnol) Vol. 11 Issue 8 Pg. 1401-17 (Aug 2015) ISSN: 1550-7033 [Print] United States
PMID26295141 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Ligands
  • Lipids
  • Nanocapsules
  • Polymers
  • Taxoids
  • tat Gene Products, Human Immunodeficiency Virus
  • Docetaxel
  • ERBB2 protein, human
  • Receptor, ErbB-2
Topics
  • Antineoplastic Agents (administration & dosage, chemistry)
  • Breast Neoplasms (drug therapy, metabolism, pathology)
  • Cell Line, Tumor
  • Diffusion
  • Docetaxel
  • Humans
  • Ligands
  • Lipids (chemistry)
  • Nanocapsules (chemistry, ultrastructure)
  • Polymers (chemistry)
  • Receptor, ErbB-2 (metabolism)
  • Taxoids (administration & dosage, chemistry)
  • Treatment Outcome
  • tat Gene Products, Human Immunodeficiency Virus (chemistry, pharmacokinetics)

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