title: Targeted multidrug-resistance reversal in tumor based on PEG-PLL-PLGA polymer nano drug delivery system.
abstract: The study investigated the reversal of multidrug resistance (MDR) and the biodistribution of nanoparticles (NPs) that target leukemia cells in a nude mice model via a surface-bound transferrin (Tf). The cytotoxic cargo of daunorubicin (DNR) and tetrandrine (Tet) was protected in the NPs by an outer coat composed of polyethylene glycol (PEG)-poly-L-lysine (PLL)-poly(lactic-co-glycolic acid) (PLGA) NPs. Injection of DNR-Tet-Tf-PEG-PLL-PLGA NPs into nude mice bearing MDR leukemia cell K562/A02 xenografts was shown to inhibit tumor growth, and contemporaneous immunohistochemical analysis of tumor tissue showed the targeted NPs induced apoptosis in tumor cells. Targeted tumor cells exhibited a marked increase in Tf receptor expression, with noticeable decreases in P-glycoprotein, MDR protein, and nuclear factor κB, as assessed by quantitative real-time polymerase chain reaction and Western blot analysis. Moreover, the concentration of DNR was shown to increase in plasma, tumor tissue, and major organs. Flow cytometry analysis with a near-infrared fluorescent (NIRF) dye, NIR797, was used to study the effectiveness of Tf as a targeting group for leukemia cells, a finding that was supported by NIRF imaging in tumor-bearing nude mice. In summary, our studies show that DNR-Tet-Tf-PEG-PLL-PLGA NPs provide a specific and effective means to target cytotoxic drugs to MDR tumor cells.
authors.affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, People's Republic of China.
authors.forename: Liting
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, People's Republic of China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, People's Republic of China ; School of Pharmacy, Nanjing University of Technology, Nanjing, People's Republic of China.
authors.forename: Yonglu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, People's Republic of China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Xia
authors.affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, People's Republic of China.
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Nanjing University of Technology, Nanjing, People's Republic of China.
authors.forename: Xueming
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Pharmacy, Nanjing University of Technology, Nanjing, People's Republic of China.
authors.forename: Haixiang
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Hulin
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, People's Republic of China.
authors.forename: Baoan
authors.initials: B
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D051379:Mice; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011107:Polylysine / Q000031:analogs & derivatives* / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011091:Polyesters; C574222:monomethoxy (polyethylene glycol)-poly(lactide-co-glycolide)-poly(lysine); D011107:Polylysine; D011092:Polyethylene Glycols
keywords: PEG-PLL-PLGA nanoparticles; multidrug resistance; tetrandrine; transferrin