title: Quantitative control of active targeting of nanocarriers to tumor cells through optimization of folate ligand density.
abstract: The active targeting delivery system has been widely studied in cancer therapy by utilizing folate (FA) ligands to generate specific interaction between nanocarriers and folate receptors (FRs) on tumor cell. However, there is little work that has been published to investigate the influence of the definite density of the FA ligands on the active targeting of nanocarriers. In this study, we have combined magnetic-guided iron oxide nanoparticles with FA ligands, adjusted the FA ligand density and then studied the resulting effects on the active targeting ability of this dual-targeting drug delivery system to tumor cells. We have also optimized the FA ligand density of the drug delivery system for their active targeting to FR-overexpressing tumor cells in vitro. Prussian blue staining, semi-thin section of cells observed with transmission electron microscopy (TEM) and inductively coupled plasma-atomic emission spectroscopy (ICP-AES) have shown that the optimal FA density is from 2.3 × 10(18) to 2.5 × 10(18) per gram nanoparticles ((g·NPs)(-1)). We have further tried to qualitatively and quantitatively control the active targeting and delivering of drugs to tumors on 4T1-bearing BALB/c mice. As expected, the in vivo experimental results have also demonstrated that the FA density of the magnetic nanoparticles (MNPs) could be optimized for a more easily binding to tumor cells via the multivalent linkages and more readily internalization through the FR-mediated endocytosis. Our study can provide a strategy to quantitatively control the active targeting of nanocarriers to tumor cells for cancer therapy.
authors.affiliation: Key Laboratory of Advanced Technologies of Material, Minister of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Key Laboratory of Advanced Technologies of Material, Minister of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Key Laboratory of Advanced Technologies of Material, Minister of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
authors.forename: Huili
authors.initials: H
authors.lastname: Sun
authors.affiliation: Key Laboratory of Advanced Technologies of Material, Minister of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Guo
authors.affiliation: Key Laboratory of Advanced Technologies of Material, Minister of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Advanced Technologies of Material, Minister of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China. Electronic address: shaobingzhou@swjtu.edu.cn.
authors.forename: Shaobing
authors.initials: S
authors.lastname: Zhou
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D005492:Folic Acid / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007501:Iron / Q000378:metabolism; D008024:Ligands; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D008297:Male; D008807:Mice, Inbred BALB C; D013050:Spectrometry, Fluorescence; D013194:Staining and Labeling; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D004337:Drug Carriers; D008024:Ligands; D058185:Magnetite Nanoparticles; D004317:Doxorubicin; D005492:Folic Acid; D007501:Iron
keywords: Active targeting; Drug delivery; Folate-mediated; Magnetic nanoparticles; Multivalent linkage