title: Tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier for targeted intracellular delivery of paclitaxel.
abstract: In the present study, we constructed a tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier containing paclitaxel (FA-BSA-LC/DOPE-PTX), by adding 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and oleic acid as pH-sensitive components into the formulation of lipid core and then coating with folic acid modified bovine serum albumin (FA-BSA) for tumor targeting activity. In vitro drug release study demonstrated that paclitaxel (PTX) was released from FA-BSA-LC/DOPE in a pH-dependent manner. The vitro cytotoxicity assays showed that all the blank nanocarriers were nontoxic. However, MTT assay showed that FA-BSA-LC/DOPE-PTX was highly cytotoxic. Cellular uptake experiments analyzed with flow cytometry and laser scan confocal microscope (LSCM) revealed that FA-BSA-LC/DOPE was taken up in great amount via folate receptor-mediated endocytosis and pH-sensitive release of drug to cytoplasm. Furthermore, the study of intracellular drug release behavior demonstrated that the FA-BSA-LC/DOPE escaped from lysosomes and released drug into cytoplasm. The in vivo targeting activity showed that the nanocarrier selectively targeted tumor and had long residence time for BSA layer increased the stability in blood. Moreover, FA-BSA-LC/DOPE-PTX produced very marked anti-tumor activity in tumor-bearing mice in vivo. Therefore, FA-BSA-LC/DOPE as biocompatible, tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier is a promising system for effective intracellular delivery of PTX to tumor.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Conghui
authors.initials: C
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Hu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Mingxi
authors.initials: M
authors.lastname: Qiao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Yinjie
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Guo
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; School of Pharmacy, Soochow University, Suzhou 215123, China. Electronic address: chendaweisd@yahoo.com.
authors.forename: Dawei
authors.initials: D
authors.lastname: Chen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D005492:Folic Acid / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles; D019301:Oleic Acid / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008055:Lipids; D010714:Phosphatidylethanolamines; D012710:Serum Albumin, Bovine; D019301:Oleic Acid; C020888:1,2-dielaidoylphosphatidylethanolamine; D005492:Folic Acid; D017239:Paclitaxel
keywords: 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine; 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (PubChem CID: 5909904); Bovine serum albumin; Folic acid; Folic acid (PubChem CID: 6037); Oleic acid (PubChem CID: 445639); Paclitaxel; Paclitaxel (PubChem CID: 44155032); Targeted intracelluar delivery; pH-sensitivity