title: The role of the cell cycle in the cellular uptake of folate-modified poly(L-amino acid) micelles in a cell population.
abstract: Nanoparticles are widely recognized as a vehicle for tumor-targeted therapies. There are many factors that can influence the uptake of nanoparticles, such as the size of the nanoparticles, and/or their shape, elasticity, surface charge and even the cell cycle phase. However, the influence of the cell cycle on the active targeting of a drug delivery system has been unknown until now. In this study, we initially investigated the folate receptor α (FR-α) expression in different phases of HeLa cells by flow cytometric and immunocytochemical methods. The results obtained showed that FR-α expression was cell cycle-dependent, i.e. the S cells' folate receptor expression was the highest as the cell progressed through its cycle. Then, we used folate modified poly(L-amino acid) micelles (FA-PM) as an example to investigate the influence of the cell cycle on the active targeting drug delivery system. The results obtained indicated that the uptake of FA-PM by cells was influenced by the cell cycle phase, and the S cells took up the greatest number of folate conjugated nanoparticles. Our findings suggest that future studies on ligand-mediated active targeting preparations should consider the cell cycle, especially when this system is used for a cell cycle-specific drug.
authors.affiliation: School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, China. lijun@ahmu.edu.cn.
authors.forename: Jihui
authors.initials: J
authors.lastname: Tang
authors.affiliation: School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, China. lijun@ahmu.edu.cn.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, China. lijun@ahmu.edu.cn.
authors.forename: Fenqi
authors.initials: F
authors.lastname: Ji
authors.affiliation: School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, China. lijun@ahmu.edu.cn.
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, China. lijun@ahmu.edu.cn.
authors.forename: Junjie
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, China. lijun@ahmu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Song
authors.affiliation: School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, China. lijun@ahmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. zhoujpcpu@126.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhou
mesh_terms: D002453:Cell Cycle / Q000187:drug effects*; D016503:Drug Delivery Systems / Q000379:methods*; D058975:Folate Receptor 1 / Q000096:biosynthesis; D006367:HeLa Cells; D006801:Humans; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology
chemical_list: D058975:Folate Receptor 1; D008823:Micelles; D010455:Peptides