title: The cellular uptake mechanism, intracellular transportation, and exocytosis of polyamidoamine dendrimers in multidrug-resistant breast cancer cells.
abstract: Polyamidoamine dendrimers, which can deliver drugs and genetic materials to resistant cells, are attracting increased research attention, but their transportation behavior in resistant cells remains unclear. In this paper, we performed a systematic analysis of the cellular uptake, intracellular transportation, and efflux of PAMAM-NH2 dendrimers in multidrug-resistant breast cancer cells (MCF-7/ADR cells) using sensitive breast cancer cells (MCF-7 cells) as the control. We found that the uptake rate of PAMAM-NH2 was much lower and exocytosis of PAMAM-NH2 was much greater in MCF-7/ADR cells than in MCF-7 cells due to the elimination of PAMAM-NH2 from P-glycoprotein and the multidrug resistance-associated protein in MCF-7/ADR cells. Macropinocytosis played a more important role in its uptake in MCF-7/ADR cells than in MCF-7 cells. PAMAM-NH2 aggregated and became more degraded in the lysosomal vesicles of the MCF-7/ADR cells than in those of the MCF-7 cells. The endoplasmic reticulum and Golgi complex were found to participate in the exocytosis rather than endocytosis process of PAMAM-NH2 in both types of cells. Our findings clearly showed the intracellular transportation process of PAMAM-NH2 in MCF-7/ADR cells and provided a guide of using PAMAM-NH2 as a drug and gene vector in resistant cells.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang.
authors.forename: Mengjun
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang; Department of Pharmaceutics, School of Pharmacy, Liaoning Medical University, Jinzhou, Liaoning Province, People's Republic of China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang.
authors.forename: Guannan
authors.initials: G
authors.lastname: Guan
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang.
authors.forename: Mingxi
authors.initials: M
authors.lastname: Qiao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang.
authors.forename: Dawei
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Hu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D050091:Dendrimers / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000493:pharmacokinetics*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009757:Nylons / Q000493:pharmacokinetics
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D050091:Dendrimers; D004337:Drug Carriers; D016650:Fluorescein-5-isothiocyanate; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009757:Nylons; C104700:PAMAM Starburst; C520550:PAMAM-G4
keywords: PAMAM dendrimers; endocytosis; exocytosis; intracellular transportation; multidrug resistance