Synthesis of anti mucin1 aptamer-armed PEGylated Gold nanoparticle for targeted delivery of PTX to breast cancer cell line

Abstract

Introduction: Developing of novel therapeutic approaches with high efficiency and precision like photothermal therapy (PTT) is essential to combat breast cancer. The gold nanoparticle (AuNPs) has shown critical ability in PTT and targeted delivery.Aims: The PTX/PEG-AuNPs@antiMUC1 could specificity attach to MUC1-positive cancer cells showed an excellenttargeted PTX delivery and efficient apoptosis in MCF-7 cancer cells when used in combination with NIR irradiation. Methods: Herein, we evolved targeted PTT in a multifunctional drug delivery platform. The AuNPs were modified by poly (ethylene glycol) (PEG) to improve their biocompatibility, and the mucin1 (MUC1) aptamer-modified PEG-AuNPs were successfully prepared. The synergistic effect of PTX/PEG-AuNPs@antiMUC1 was also evaluated in this research.Results: The Paclitaxel (PTX)–loaded PEG-AuNPs@antiMUC1 system displayed a dual NIR/pH-dependent sustained release. In vitro cell cytotoxicity experiments on MUC1-positive and MUC1-negative breast cancer cells showed the desired selectivity of the prepared system towards MUC1-positive cells. The capability of the PTX/PEG-AuNPs@antiMUC1 in combination with near-infrared (NIR) irradiation in ablation of MUC1-positive cancer cells with excellent cellular uptake was also observed. Furthermore, simultaneous utilization of PTT and targeted drug delivery indicated a synergistic effect that increased cell death versus seldom PTT or chemotherapy. The protein expression analysis confirmed that the increased expression of the apoptotic Caspase3. It declined in terms of the anti-apoptotic Bcl-xL in the presence of the prepared synergistic combinational system, which showed its high potential in cancer therapy. Conclusion: The experimental results showed that synergistic therapy of PTX/PEG-AuNPs@antiMUC1 caused effective death of MUC1-positive cells mediated by heat generation and activated apoptotic pathways. Therefore, NIR-light-responsive PTX/PEG-AuNPs@antiMUC1 can be a hopeful photothermal agent for breast cancer treatment.