title: Enhanced therapeutic effect of Adriamycin on multidrug resistant breast cancer by the ABCG2-siRNA loaded polymeric nanoparticles assisted with ultrasound.
abstract: The overexpression of the breast cancer resistance protein (ABCG2) confers resistance to Adriamycin (ADR) in breast cancer. The silencing of ABCG2 using small interfering RNA (siRNA) could be a promising approach to overcome multidrug resistance (MDR) in cancer cells. To deliver ABCG2-siRNA effectively into breast cancer cells, we used mPEG-PLGA-PLL (PEAL) nanoparticles (NPs) with ultrasound-targeted microbubble destruction (UTMD). PEAL NPs were prepared with an emulsion-solvent evaporation method. The NPs size was about 131.5 ± 6.5 nm. The siRNA stability in serum was enhanced. The intracellular ADR concentration increased after the introduction of siRNA-loaded NPs. After intravenous injection of PEAL NPs in tumor-bearing mice, the ABCG2-siRNA-loaded NPs with UTMD efficiently silenced the ABCG2 gene and enhanced the ADR susceptibility of MCF-7/ADR (ADR resistant human breast cancer cells). The siRNA-loaded NPs with UTMD + ADR showed better tumor inhibition effect and good safety in vivo. These results indicate that ADR-chemotherapy in combination with ABCG2-siRNA is an attractive strategy to treat breast cancer.
authors.affiliation: Department of Ultrasound, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Bai
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, People's Republic of China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Teng
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Ultrasound, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, People's Republic of China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, People's Republic of China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, People's Republic of China.
authors.forename: Yourong
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Department of Ultrasound, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, People's Republic of China.
authors.forename: Lianfang
authors.initials: L
authors.lastname: Du
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology*; D004317:Doxorubicin / Q000008:administration & dosage*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D020287:In Situ Nick-End Labeling; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D011091:Polyesters; D011092:Polyethylene Glycols; D034741:RNA, Small Interfering / Q000008:administration & dosage; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014463:Ultrasonography; D023041:Xenograft Model Antitumor Assays
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D011091:Polyesters; D034741:RNA, Small Interfering; C558447:methoxypolyethyleneglycol-poly(lactic-co-glycolic acid); D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: UTMD; combination therapy; gene silencing; siRNA delivery; xenograft nude mice model