Preparation of Lipid Microbubble/Paclitaxel Nanoparticle Complex and Its In Vitro Antigastric Tumor Effect Mediating the STAT3-NF-κB Pathway

Abstract

In this research, lipid microbubbles (MBs) were prepared first, and then Tat peptide, carboxylated heparin, amino biotin, and amino folic acid were successively synthesized. After a certain amount of paclitaxel was added, paclitaxel nanoparticles (NPs) with a double-ligand were obtained through reaction. The lipid MBs prepared above were added to streptavidin. After washing and purification, the lipid MBs and double-ligand paclitaxel NPs were added. After incubation on ice, the lipid MB-double-ligand paclitaxel NP complex was obtained. In addition to the physical characterization of the materials, human breast cancer cells MDA-MB-231 and lung cancer cells A549 were first utilized to test the biological properties of the NP complex In Vitro and then utilized to study the effects of gastric cancer (GC) cells. The results revealed that the lipid MBs were uniformly distributed and did not aggregate. The concentration of the NP complex reached 7.75±0.93×108 NPs/mL, and the particle size was 2.23±0.68 μm. At various radiation intensities, blue fluorescently stained MDA-MB-231 cells and A549 cells showed greener fluorescently labeled double-ligand paclitaxel NPs around and inside the nucleus of Hoechst 33342. According to the prepared products and byproducts, they were grouped to compare different prepared products. The fluorescence uptake of the two cells at 4 h was the highest under the condition of the NP complex combined with ultrasonic radiation, and the destruction of cancer cells (MDA-MB-231 and A549) was the strongest under the condition of the NP complex combined with ultrasonic radiation. In GC cells, NP complexes inhibited cell migration and invasion relative to the other groups (P <0.05), the level of Bax protein increased (P <0.05), while that of Bcl-2, pSTAT3/STAT3, and phosphorylation of NF-kappa B (PNF-κB)/NF-κB protein were markedly decreased (P <0.05).