Aptamer-conjugated PLA-PEG nanoparticles for delivery of doxorubicin to liver cancer.

PolyScitech (www.polyscitech.com) provides a wide array of functionalized PLA/PLGA-PEG block copolymers with –COOH, Maleimide, -NHS, bromoacetamide, and other PEG terminus functionality for conjugation to targeting ligands and aptamers. Recently these types of polymers were conjugated to tumor-specific aptamer TLS11a and utilized in nanoparticle form to deliver doxorubicin to liver cancer cells.  Read more: Shannon E. Weigum ; Melissa Sutton ; Eugenia Barnes ; Sarah Miller and Tania Betancourt "Targeting hepatocellular carcinoma with aptamer-functionalized PLGA/PLA-PEG nanoparticles", Proc. SPIE 9166, Biosensing and Nanomedicine VII, 916605 (August 27, 2014); doi:10.1117/12.2062283; http://dx.doi.org/10.1117/12.2062283

“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. Topics: Liver cancer ; Nanoparticles ; Polymers ; Cell death ; Proteins ; Luminescence ; Cancer ; Colorimetry ; Confocal microscopy”