title: 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.
authors: Zhe
authors: Z
authors: Yang
authors: Wenxin
authors: W
authors: Tang
authors: Xingen
authors: X
authors: Luo
authors: Xiaofang
authors: X
authors: Zhang
authors: Chao
authors: C
authors: Zhang
authors: Hao
authors: H
authors: Li
authors: Di
authors: D
authors: Gao
authors: Huiyan
authors: H
authors: Luo
authors: Qing
authors: Q
authors: Jiang
authors: Jie
authors: J
authors: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004058:Diffusion; D000077143:Docetaxel; D006801:Humans; D008024:Ligands; D008055:Lipids / Q000737:chemistry; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D011108:Polymers / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D000970:Antineoplastic Agents; D000077143:Docetaxel; D008024:Ligands; D008055:Lipids; D053769:Nanocapsules; D011108:Polymers; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D054322:tat Gene Products, Human Immunodeficiency Virus; C508053:ERBB2 protein, human