Targeting Hepatocellular Carcinoma with Aptamer-functionalized PLGA/PLA-PEG Nanoparticles
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Date
2014-08-27
Authors
Weigum, Shannon E.
Sutton, Melissa
Barnes, Eugenia
Miller, Sarah
Betancourt, Tania
Journal Title
Journal ISSN
Volume Title
Publisher
Society of Photo-optical Instrumentation Engineers
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, particularly in regions where chronic Hepatitis B and C infections are common. Nanoparticle assemblies that incorporate high-affinity aptamers which specifically bind malignant hepatocellular carcinoma cells could be useful for targeted drug delivery or enhancing contrast with existing ablation therapies. The in vitro interactions of a tumor-specific aptamer, TLS11a, were characterized in a hepatoma cell line via live-cell fluorescence imaging, SDS-PAGE and Western Blotting techniques. Cell surface binding of the aptamer-AlexaFluor® 546 conjugate was found to occur within 20 minutes of initial exposure, followed by internalization and localization to late endosomes or lysosomes using a pH-sensitive LysoSensor™ Green dye and confocal microscopy. Aptamer-functionalized polymer nanoparticles containing poly(lactic-co-glycolic acid) (PLGA) and poly(lactide)-b-poly(ethylene glycol) (PLA-PEG) were then prepared by nanoprecipitation and passively loaded with the chemotherapeutic agent, doxorubicin, yielding spherical nanoparticles approximately 50 nm in diameter. Targeted drug delivery and cytotoxicity was assessed using live/dead fluorescent dyes and a MTT colorimetric viability assay with elevated levels of cell death found in cultures treated with either the aptamer-coated and uncoated polymer nanoparticles. Identification and characterization of the cell surface protein epitope(s) recognized by the TLS11a aptamer are ongoing along with nanoparticle optimization, but these preliminary studies support continued investigation of this aptamer and functionalized nanoparticle conjugates for targeted labeling and drug delivery within malignant hepatocellular carcinomas.
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Keywords
cancer, hepatocellular carcinoma, aptamer, nanoparticles, drug delivery
Citation
Weigum, S. E., Sutton, M., Barnes, E., Miller, S., & Betancourt, T. (2014). Targeting hepatocellular carcinoma with aptamer-functionalized PLGA/PLA-PEG nanoparticles. Proceedings of the SPIE, Biosensing and Nanomedicine VII, 916605.
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© 2014 SPIE.