AS1411 Aptamer-Decorated Biodegradable Polyethylene Glycol-Poly(lactic-co-glycolic acid) Nanopolymersomes for the Targeted Delivery of Gemcitabine to Non-Small Cell Lung Cancer In Vitro

作者：Alibolandi Mona; Ramezani Mohammad; Abnous Khalil^*; Hadizadeh Farzin^*

来源：Journal of Pharmaceutical Sciences, 2016, 105(5): 1741-1750.

DOI：10.1016/j.xphs.2016.02.021

• cancer chemotherapy
• drug delivery system
• encapsulation
• nanoparticle
• PLGA
• polymeric drug delivery systems
• targeted drug delivery

Molecularly targeted drug delivery systems represent a novel therapeutic strategy in the treatment of different cancers. In the present study, we have developed gemcitabine (GEM)-loaded AS1411 aptamer surface-decorated polyethylene glycol-poly(lactic-co-glycolic acid) nanopolymersome (Apt-GEM-NP) to target nucleolin-overexpressing non-small cell lung cancer (NSCLC; A549). The prepared Apt-GEM-NP showed average particle size of 128 +/- 5.23 nm and spherical morphology with encapsulation efficiency and loading content of 95.32 +/- 2.37% and 8.61 +/- 0.27%, respectively. Apt-GEM-NP exhibited a controlled release pattern. A sustained release of drug in physiological conditions will greatly improve the chemotherapeutic efficiency of a system. Enhanced cellular uptake and the cytotoxicity of aptamer-conjugated nanoparticles (NPs) in A549 cancer cells obviously verified nucleolin-mediated receptor-based active targeting. Nucleolin-mediated internalization of the targeted polymeric NP was further confirmed by flow cytometry and fluorescence microscopy. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay clearly showed the enhanced cell proliferation inhibitory effect of AS1411-conjugated NP on account of the selective delivery of GEM to the nucleolin-overexpressing cancer cells. Our results showed that AS1411 aptamer conjugation on the surface of NP could be a potential treatment strategy for A549 as a nucleolin-overexpressing cell line. This suggests that AS1411-GEM-NPs could be potentially used for the treatment of NSCLC.

• 出版日期2016-5