Hanafi-Bojd Mohammad Yahya, Moosavian Kalat Seyedeh Alia, Taghdisi Seyed Mohammad, Ansari Legha, Abnous Khalil, Malaekeh-Nikouei Bizhan
a Cellular and Molecular Research Center, Department of Pharmacology, School of Medicine , Birjand University of Medical Sciences , Birjand , Iran.
b Nanotechnology Research Center , Mashhad University of Medical Sciences , Mashhad , Iran.
Drug Dev Ind Pharm. 2018 Jan;44(1):13-18. doi: 10.1080/03639045.2017.1371734. Epub 2017 Sep 6.
In the present study, we developed aptamer (Apt) conjugated mesoporous silica nanoparticles (MSNs) for specific delivery of epirubicin (EPI) to breast cancer cells. MSNs were synthesized and functionalized with 3-mercaptopropyltrimethoxysilane (3-MPTMS), followed by MUC1 aptamer conjugation through disulfide bonds. The nanoparticles were analyzed by transmission electron microscopy (TEM), particle size analyzer, zeta potential, elemental analysis (CHNS), aptamer conjugation efficiency, drug loading efficiency, and drug release profile. Cell uptake and in vitro cytotoxicity of different formulations were performed. The results of MSNs characterization confirmed spherical nanoparticles with thiol functional groups. Particle size of obtained nanoparticles was 163 nm in deionized water. After conjugation of MUC1 aptamer and EPI loading (MSN-MUC1-EPI), particle size increased to 258 nm. The aptamer conjugation to MSNs with disulfide bonds were confirmed using gel retardation assay. Cellular uptake studies revealed better cell uptake of MSN-MUC1-EPI compared to MSN-EPI. Moreover, cytotoxicity study results in MCF7 cell lines showed improved cytotoxicity of MSN-MUC1-EPI in comparison with MSN-EPI or EPI at the same concentration of drug. These results exhibited that MSN-MUC1-EPI has the potential for targeted drug delivery into MUC1 positive breast cancer cells to improve drug efficacy and alleviate side effects.
在本研究中，我们开发了适配体（Apt）偶联的介孔二氧化硅纳米颗粒（MSNs），用于将表柔比星（EPI）特异性递送至乳腺癌细胞。合成了MSNs并用3-巯基丙基三甲氧基硅烷（3-MPTMS）进行功能化，随后通过二硫键偶联MUC1适配体。通过透射电子显微镜（TEM）、粒度分析仪、zeta电位、元素分析（CHNS）、适配体偶联效率、载药效率和药物释放曲线对纳米颗粒进行了分析。对不同制剂进行了细胞摄取和体外细胞毒性实验。MSNs表征结果证实了具有硫醇官能团的球形纳米颗粒。在去离子水中获得的纳米颗粒粒径为163nm。在偶联MUC1适配体并加载EPI（MSN-MUC1-EPI）后，粒径增加到258nm。使用凝胶阻滞试验证实了通过二硫键将适配体偶联到MSNs上。细胞摄取研究表明，与MSN-EPI相比，MSN-MUC1-EPI具有更好的细胞摄取能力。此外，在MCF7细胞系中的细胞毒性研究结果表明，在相同药物浓度下，MSN-MUC1-EPI与MSN-EPI或EPI相比，细胞毒性有所提高。这些结果表明，MSN-MUC1-EPI具有将药物靶向递送至MUC1阳性乳腺癌细胞的潜力，以提高药物疗效并减轻副作用。
