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Biotinylated polyurethane-urea nanoparticles for targeted theranostics in human hepatocellular carcinoma

Nano Research 2015年第5期8卷 1729-1745页

作者： Genoveva MorraI-Ruiz Pedro Melgar-Lesmes Andrea Lopez-Vicente conxita solans Maria Jose Garcia-Celma Department of Pharmacy and Pharmaceutical Technology Faculty of Pharmacy University of Barcelona Av Joan XXIII s/n 08028 Barcelona Spain Institute of Advanced Chemistry of Catalonia (IQAC) CS/C Jordi Girona 18-26 08034 Barcelona Spain Networking Research Center on Bioengineering Biomaterials and Nanomedicine CIBER-BBN Spain

Over the past years, significant efforts have been devoted to explore novel drug delivery and detection strategies for simultaneous therapy and diagnostics. The development of biotinylated polyurethane-urea nanoparticles as theranostic nanocarriers for targeted drug and plasmid delivery, for fluorescence detection of human hepatocellular carcinoma cells, is described herein. These targeted nanoparticles are specifically designed to incorporate biotin into the polymeric matrix, since many tumor types overexpress receptors for biotin as a mechanism to boost uncontrolled cell growth. The obtained nanoparticles were spherical, exhibited an average diameter ranging 110-145 nm, and showed no cytotoxicity in healthy endothelial cells. Biotinylated nanoparticles are selectively incorporated into the perinuclear and nuclear area of the human hepatocellular carcinoma cell line, HepG2, in division, but not into growing, healthy, human endothelial cells. Indeed, the simultaneous incorporation of the anticancer drugs, phenoxodiol or sunitinib, together with plasmid DNA encoding green fluorescent protein, into these nanoparticles allows a targeted pharmacological antitumor effect and furthermore, selective transfection of a reporter gene, to detect these cancer cells. The combined targeted therapy and detection strategy described here could be exploited for liver cancer therapy and diagnostics, with a moderate safety profile, and may also be a potential tool for other types of cancer.

关键词： cancer therapy DNA nanoparticles polyurethane theranostics

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