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Targeted therapy of hepatocellular carcinoma with aptamer-functionalized biodegradable nanoparticles

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Abstract

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, occurring primarily in regions where viral hepatitis infections are common. Unfortunately, most HCC cases remain undiagnosed until late stages of the disease when patient outcome is poor, typically limiting survival from a few months to a year after initial diagnosis. In order to better care for HCC patients, new target-specific approaches are needed to improve early detection and therapeutic intervention. In this work, polymeric nanoparticles functionalized with a HCC-specific aptamer were examined as potential targeted drug delivery vehicles. Specifically, doxorubicin-loaded nanoparticles were prepared via nanoprecipitation of blends of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol). These particles were further functionalized with the HCC-specific TLS11a aptamer. The in vitro interaction and therapeutic efficacy of the aptamer and aptamer-functionalized nanoparticles were characterized in a hepatoma cell line. Nanoparticles were found to be spherical in shape, roughly 100–125 nm in diameter, with a low polydispersity (≤0.2) and slightly negative surface potential. Doxorubicin was encapsulated within the particles at ~40 % efficiency. Drug release was found to occur through anomalous transport influenced by diffusion and polymer relaxation, releasing ~50 % doxorubicin in the first 10 h and full release occurring within 36 h. Confocal microscopy confirmed binding and attachment of aptamer-targeted nanoparticles to the cell surface of cultured HCC cells. Efficacy studies demonstrated a significant improvement in doxorubicin delivery and cell-killing capacity using the aptamer-functionalized, drug-loaded nanoparticles versus controls further supporting use of aptamer nanoparticles as a targeted drug delivery system for HCC tumors.

In this work, polymeric nanoparticles functionalized with a liver cancer-specific aptamer were examined as potential targeted drug delivery vehicles. The aptamer-functionalized nanoparticles were found to significantly improve doxorubicin drug delivery and cell-killing capacity in vitro versus non-targeted controls, supporting their use as a targeted treatment toward liver cancer tumors.

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Acknowledgments

This research was supported in part by the Texas Emergent Technology Fund (start-up funds to TB), the Robert A. Welch Foundation (AI-0045), NIGMS South Texas Doctoral Bridge Program (R25-GM102783) fellowship to C. Munoz, and Texas State University (start-up funds to SW).

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Authors and Affiliations

  1. Department of Biology, Texas State University, San Marcos, TX, USA

    Shannon Weigum

  2. Materials Science, Engineering, and Commercialization Program, Texas State University, San Marcos, TX, USA

    Shannon Weigum, Travis Cantu & Tania Betancourt

  3. Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX, USA

    Elizabeth McIvor, Christopher Munoz, Richard Feng, Kyle Walsh & Tania Betancourt

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  1. Shannon Weigum
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  2. Elizabeth McIvor
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  3. Christopher Munoz
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  4. Richard Feng
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  5. Travis Cantu
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  6. Kyle Walsh
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  7. Tania Betancourt
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Correspondence to Shannon Weigum or Tania Betancourt.

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Weigum, S., McIvor, E., Munoz, C. et al. Targeted therapy of hepatocellular carcinoma with aptamer-functionalized biodegradable nanoparticles. J Nanopart Res 18, 341 (2016). https://doi.org/10.1007/s11051-016-3633-5

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