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.

Enhanced Sensitivity of Cancer Stem Cells to Chemotherapy Using Functionalized Mesoporous Silica Nanoparticles

“…ABCG2 gene silencing using short hairpin RNA (shRNA) is a promising therapeutic approach for overcoming drug resistance [12][13][14] . Nanoparticle-mediated gene delivery has demonstrated enhanced transfection efficacy due to the structure, size, and surface properties of the nanoparticles 15,16 , allowing them to readily accumulate in and be retained by solid tumors through the enhanced permeability and retention (EPR) effect 17,18 .…”

MicroRNA-200c delivered by solid lipid nanoparticles enhances the effect of paclitaxel on breast cancer stem cell

“…17,18 Therefore, the development of safe and efficient miRNA carriers is a prerequisite for the success of combination therapy. Currently, the combination of gene and chemical drugs can be classified into three categories: 1) chemotherapy combined with gene carrying nanoparticles; 19 2) codelivery; 20 and 3) use of multiple nanocarriers. 21 Using separate delivery systems has the advantage of controlling timing and dosage regimen for the chemo and gene drugs.…”

Gas‑filled ultrasound microbubbles enhance the immunoactivity of the HSP70‑MAGEA1 fusion protein against MAGEA1‑expressing tumours

“…Microbubbles coupled with ultrasound exposure have been studied for opening the blood-brain barrier (BBB) and delivering drugs ( 36 – 38 ). Combining siRNA silencing ABCG2-loaded mPEG-PLGA-PLL nanoparticles and ultrasound-targeted Microbubbles destruction enhanced therapeutic effect of Adriamycin on multidrug-resistant breast cancer ( 39 ). Thrombus-targeting Microbubbles, which have fibrinolytic drugs on the surface reduced the size of the thrombus via ultrasound imaging without prolonging bleeding time ( 40 ).…”