Doxorubicin And Iron Oxide Nanoparticles Loaded Microbubbles:Dual-mode Imaging And Its Cytotoxic Effect On Lymphoma Cells In Vitro

Objective:To fabricate a kind of multifunctional polymer microbubbles(MPMBs) loaded with doxorubicin (DOX/ADM) and iron oxide nanoparticles (ION). To investigate its dual-mode imaging ability, and observe its effect on cell proliferation and apoptosis in SU-DHL-4 cells and discuss the possible mechanism.Methods:The MPMBs were effectively synthesized with polylactic acid (PLA) and polyvinyl alcohol (PVA) via mechanical vibration method. The physical properties were measured, such as morphology, the diameter size, the drug-loading efficiency, etc. Enhancement of ultrasound (US)/magnetic resonance (MR) imaging were evaluated in vitro. SU-DHL-4 cells were divided into six groups (Control, Ultrasound, ADM, ADM+ultrasound, MPMBs and MPMBs+ultrasound) according to different treatments.Cell proliferation Was evaluated using the Cell Counting Kit-8 (CCK-8) assay and apoptosis was assessed by flow cytometry. Western bloting technology was used to detect expression levels of apoptosis regulating proteins, including bcl-2, bax and caspase 3.The morphologic changes were detected by AO/EB staining.Results:The MPMBs were spherical and their mean size was (603.3± 190.8) nm, and the doxorubicin encapsulation efficiency was (25.41±4.52)%. US/MR dual-mode imaging showed its better property compared with ordinary polymer microbubbles (PMBs). Besides, Stronger proliferation inhibition and apoptosis induction effect on SU-DHL-4 cells,compared with the control group and the ultrasound group,was observed in other groups, in which protein expression of bcl-2 was downregulated while bax and caspase3 were upregulated to some extent.Changes mentioned above of group "MPMBs+ultrasound" were more significant than that of group "ADM" through pairwise comparison.Conclusion:MPMBs loaded with doxorubicin and iron oxide nanoparticles can increase the effect of US/ MR imaging in vitro. When combined with US. MPMBs can enhance cytotoxicity of ADM to DLBCL cells.This study offers some experimental evidence and bebeneficial help for further researches.