Enhanced therapeutic effect of Adriamycin on multidrug resistant breast cancer by the ABCG2-siRNA loaded polymeric nanoparticles assisted with ultrasound
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Min Bai1,*, Ming Shen2,*, Yanwei Teng2, Ying Sun2, Fan Li1, Xiangyu Zhang2, Yuanyuan Xu2, Yourong Duan2, Lianfang Du1
1Department of Ultrasound, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, People's Republic of China
2State 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
*These authors have contributed equally to this work
Yourong Duan, e-mail: [email protected]
Lianfang Du, e-mail: [email protected]
Keywords: siRNA delivery, UTMD, gene silencing, combination therapy, xenograft nude mice model
Received: June 10, 2015 Accepted: October 30, 2015 Published: November 09, 2015
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.
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