Targeting Hepatocellular Carcinoma with Aptamer-functionalized PLGA/PLA-PEG Nanoparticles

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dc.contributor.authorWeigum, Shannon E.
dc.contributor.authorSutton, Melissa
dc.contributor.authorBarnes, Eugenia
dc.contributor.authorMiller, Sarah
dc.contributor.authorBetancourt, Tania
dc.date.accessioned2020-05-26T18:37:28Z
dc.date.available2020-05-26T18:37:28Z
dc.date.issued2014-08-27
dc.description.abstractHepatocellular 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.
dc.description.departmentBiology
dc.description.departmentChemistry and Biochemistry
dc.description.departmentMaterials Science, Engineering, and Commercialization
dc.formatText
dc.format.extent11 pages
dc.format.medium1 file (.pdf)
dc.identifier.citationWeigum, 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.
dc.identifier.doihttps://doi.org/10.1117/12.2062283
dc.identifier.urihttps://hdl.handle.net/10877/10314
dc.language.isoen
dc.publisherSociety of Photo-optical Instrumentation Engineers
dc.rights.holder© 2014 SPIE.
dc.sourceSociety of Photo-optical Instrumentation Engineers (SPIE) NanoScience + Engineering, 2014, San Diego, California, United States.
dc.subjectcancer
dc.subjecthepatocellular carcinoma
dc.subjectaptamer
dc.subjectnanoparticles
dc.subjectdrug delivery
dc.titleTargeting Hepatocellular Carcinoma with Aptamer-functionalized PLGA/PLA-PEG Nanoparticles
dc.typeArticle

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