Expression Of Muc1 Targeted Anti-tumor Drug-loaded Nanoparticles And Its Effect In Vitro Assessment

MUC1 protein is an attractive target for anticancer drug delivery owing to its over expression in most adenocarcinomas. In this study, a MUC1-targeted drug delivery system was constructed and characterized by conjugating a MUC1 aptamer to paclitaxel (PTX) loaded poly (lactic-co-glycolic-acid) (PLGA) nanoparticles. Moreover, we evaluated the specificity and cytotoxicity of the MUCl-targeted delivery system towards MUC1+MCF-7 cells (breast cancer) and MUC1 HepG2 (hepatic cancer) cells in vitro. The results are as follows:1. Construction and characterization of the MUC 1-targeted nanoparticle:PTX loaded PLGA nanoparticles were formulated by an emulsion/evaporation method, and MUC1 aptamers (Apt) were conjugated to the particle surface through a DNA spacer. The particle size was determined by dynamic light scattering. The encapsulation efficiency and the conjugation efficiency were evaluated by UV spectroscopy. The results showed that the aptamer conjugated nanoparticles (Apt-NPs) were about 225.3±9.2 nm in size, and the encapsulation efficiency was 83.6±1.7%, each nanoparticle was estimated to have 120 aptamers conjugated to it.2. Evaluation of the nanoparticle uptake selectivity by MUC1+cancer cells:Using MCF-7 breast cancer cell as a MUC1-overexpressing model, the MUC1 aptamer increased the uptake of nanoparticles into the target cells as measured by flow cytometry. The confocal images indicated that the nanoparticles were internalized into the cells and distributed in the cytoplasm.3. Evaluation of the cytotoxicity against MUC1+cancer cells by MUC1-targeted nanoparticles:The PTX loaded Apt-NPs enhanced in vitro drug delivery and cellular toxicity to MUC1+cancer cells, as compared with non-targeted nanoparticles that without the MUC1 aptamer (P< 0.01). The IC50 of MUC 1-targeted nanoparticles against MCF-7 cells was 1.52μg/ml, while that of non-targeted nanoparticle was 4.10μg/ml.In this study, we designed a MUC1-targeted drug delivery system to enhance the delivery of paclitaxel to MUC1-overexpressing tumor cells. The constructed MUC1-targeted drug delivery system demonstrated stable biochemistry properties, high specificity and enhanced cytotoxicity towards MUC1+cancer cells in vitro. The behavior of this novel aptamer-nanoparticle bioconjugates suggests that MUC1 aptamer may potentially serve as a targeting agent and have prospective applications in targeted drug delivery towards various types of MUC1-overexpressing tumors.