title: Co-administration of dual-targeting nanoparticles with penetration enhancement peptide for antiglioblastoma therapy.
abstract: Chemotherapy is an indispensable auxiliary treatment for glioma but highly limited by the existence of both blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). The dysfunctional brain tumor blood vessels and high interstitial pressure in glioma also greatly hindered the accumulation and deep penetration of chemotherapeutics into the glioma. Lactoferrin (Lf), with its receptor overexpressed on both the brain endothelial cells and glioma cells, was here functionalized to the surface of poly(ethylene glycol)-poly(lactic acid) nanoparticles to mediate BBB/BBTB and glioma cell dual targeting. tLyP-1, a tumor-homing peptide, which contains a C-end Rule sequence that can mediate tissue penetration through the neuropilin-1-dependent internalization pathway, was coadministrated with Lf-functionalized nanoparticles (Lf-NP) to enhance its accumulation and deep penetration into the glioma parenchyma. Enhanced cellular association in both BCEC and C6 cells, increased cytotoxicity of the loaded paclitaxel, and deep penetration in the 3D glioma spheroids was achieved by Lf-NP. Following coadministration with tLyP-1, the functionalized nanoparticles obtained improved tumor targeting, glioma vascular extravasation, and antiglioma efficacy. The findings here suggested that the strategy by coadministrating BBB/BBTB and glioma cells dual-targeting nanocarriers with a tumor penetration enhancement peptide represent a promising platform for antiglioma drug delivery.
authors.affiliation: Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai, 201203, P. R. China.
authors.forename: Deyu
authors.initials: D
authors.lastname: Miao
authors.forename: Mengyin
authors.initials: M
authors.lastname: Jiang
authors.forename: Zhongyang
authors.initials: Z
authors.lastname: Liu
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Gu
authors.forename: Quanyin
authors.initials: Q
authors.lastname: Hu
authors.forename: Ting
authors.initials: T
authors.lastname: Kang
authors.forename: Qingxiang
authors.initials: Q
authors.lastname: Song
authors.forename: Lei
authors.initials: L
authors.lastname: Yao
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Gao
authors.forename: Mingjiang
authors.initials: M
authors.lastname: Sun
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007773:Lactates / Q000737:chemistry*; D007781:Lactoferrin / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018874:Spheroids, Cellular; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007773:Lactates; C533969:LyP-1 peptide; D010456:Peptides, Cyclic; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols; D007781:Lactoferrin; D017239:Paclitaxel