title: Anti-tumor activity of paclitaxel through dual-targeting lipoprotein-mimicking nanocarrier.
abstract: In the present study, we devised a strategy that paclitaxel (PTX) with lipid and octadecylamine were prepared to lipid nanoparticle (PTX-LNP) with positive charge, folic acid-modified bovine serum albumin (FB)-coated surface of PTX-LNP through electrostatic attraction and generated the lipoprotein-mimicking nanocomplex (FB-PTX-LNP) for dual-targeting therapy. Bovine serum albumin (BSA) was used as the protein model due to its specific targeting to tumor by increased transendothelial gp60-mediated transport and increased intratumoral accumulation as a result of the secreted protein, acidic and rich in cysteine (SPARC)-albumin interaction. The further conjugating folic acid to BSA achieved the dual active targeting. In vitro cytotoxicity tests suggested FB-PTX-LNP and BSA-PTX-LNP exhibited significantly higher cytotoxic activity against MCF-7 and HepG2 cells compared to PTX-LNP. The cellular uptake experiments indicated that FB-coumarin-6-LNP modified with dual-targeting had a faster and greater cellular uptake when compared to BSA-coumarin-6-LNP and coumarin-6-LNP by MCF-7 cells. Thus, both BSA and FA did play roles in in vitro cytotoxicity and cellular uptake. Furthermore, the targeting ability and therapeutic efficacy of FB-PTX-LNP were assessed in vivo. FB-PTX-LNP produced very marked targeting ability and anti-tumor activity in MDA-MB-231 tumor-bearing mice. These results indicate the protein-lipid nanocomplex FB-PTX-LNP is a potential nanocarrier for Paclitaxel dual-targeting to tumor.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Conghui
authors.initials: C
authors.lastname: Chen
authors.forename: Haiyang
authors.initials: H
authors.lastname: Hu
authors.forename: Mingxi
authors.initials: M
authors.lastname: Qiao
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhao
authors.forename: Yinjie
authors.initials: Y
authors.lastname: Wang
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.forename: Dawei
authors.initials: D
authors.lastname: Chen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D001692:Biological Transport; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D016503:Drug Delivery Systems; D005260:Female; D005492:Folic Acid / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry*; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000493:pharmacokinetics; D012795:Sialoglycoproteins / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008074:Lipoproteins; D012795:Sialoglycoproteins; C065610:sialoglycoprotein gp60; D012710:Serum Albumin, Bovine; D005492:Folic Acid; D017239:Paclitaxel
keywords: Anti-tumor efficacy; bovine serum albumin; dual-targeting; folic acid; paclitaxel