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Aptamer-labeled PLGA nanoparticles for targeting cancer cells.
Cancer Nanotechnology ( IF 4.5 ) Pub Date : 2012-01-19 , DOI: 10.1007/s12645-011-0024-6
Athulya Aravind 1 , Saino Hanna Varghese 1 , Srivani Veeranarayanan 1 , Anila Mathew 1 , Yutaka Nagaoka 1 , Seiki Iwai 1 , Takahiro Fukuda 1 , Takashi Hasumura 1 , Yasuhiko Yoshida 1 , Toru Maekawa 1 , D Sakthi Kumar 1
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Cancer is one of the leading causes of death in most parts of the world and is a very serious cause of concern particularly in developing countries. In this work, we prepared and evaluated the aptamer-labeled paclitaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Apt-PTX-PLGA NPs) which can ameliorate drug bioavailability and enable accurate drug targeting to cancer cells with controlled drug release for cancer therapy. Paclitaxel-loaded PLGA nanoparticles (PTX-PLGA NPs) were formulated by a single-emulsion/solvent evaporation method and were further surface-functionalized with a chemical cross-linker bis(sulfosuccinimidyl) suberate (BS3) to enable binding of aptamer on to the surface of the nanoparticles. The prepared nanoparticles were characterized by atomic force microscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. Cytotoxicity studies were carried out using normal human mammary epithelial cells (HMEC cells) and human glial cancer cells (GI-1 cells) by methylthiazolyldiphenyl-tetrazolium bromide assay and Alamar blue assay, which confirmed that PTX-PLGA NPs with aptamer conjugation (Apt-PTX-PLGA NPs) were comparatively non-toxic to HMEC cells while toxic to GI-1 cancer cells. Cellular uptake of PTX-PLGA NPs with and without aptamer conjugation was studied using GI-1 cells and monitored by confocal microscopy and phase contrast microscopy. Our studies demonstrated significant internalization and retention of nanoparticles inside the cells, inducing apoptosis. The preferential accumulation of PTX-PLGA NPs within the cancer cells were also confirmed by flow cytometry-based uptake studies. The results indicated that Apt-PTX-PLGA NPs could be a promising targeted therapeutic delivery vehicle for cancer treatment.
更新日期:2012-01-19
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