In vitro evaluation of biodegradable lignin-based nanoparticles for drug delivery and enhanced antiproliferation effect in cancer cells

Patrícia Figueiredo, Kalle Lintinen, Alexandros Kiriazis, Ville Hynninen, Zehua Liu, Tomás Bauleth-Ramos, Antti Rahikkala, Alexandra Correia, Tomáš Kohout, Bruno Sarmento, Jari Yli-Kauhaluoma, Jouni Hirvonen, Olli Ikkala, Mauri A. Kostiainen, Hélder A. Santos*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

107 Citations (Scopus)

Abstract

Currently, nanosystems have been developed and applied as promising vehicles for different biomedical applications. We have developed three lignin nanoparticles (LNPs): pure lignin nanoparticles (pLNPs), iron(III)-complexed lignin nanoparticles (Fe-LNPs), and Fe3O4-infused lignin nanoparticles (Fe3O4-LNPs) with round shape, narrow size distribution, reduced polydispersity and good stability at pH 7.4. The LNPs showed low cytotoxicity in all the tested cell lines and hemolytic rates below 12% after 12 h of incubation. Additionally, they induced hydrogen peroxide production in a small extent and time-dependent manner, and the interaction with the cells increased over time, exhibiting a dose-dependent cell uptake. Concerning the drug loading, pLNPs showed the capacity to efficiently load poorly water-soluble drugs and other cytotoxic agents, e.g. sorafenib and benzazulene (BZL), and improve their release profiles at pH 5.5 and 7.4 in a sustained manner. Furthermore, the BZL-pLNPs presented an enhanced antiproliferation effect in different cells compared to the pure BZL and showed a maximal inhibitory concentration ranging from 0.64 to 12.4 μM after 24 h incubation. Overall, LNPs are promising candidates for drug delivery applications, and the superparamagnetic behavior of Fe3O4-LNPs makes them promising for cancer therapy and diagnosis, such as magnetic targeting and magnetic resonance imaging.

Original languageEnglish
Pages (from-to)97-108
Number of pages12
JournalBiomaterials
Volume121
DOIs
Publication statusPublished - 1 Mar 2017
MoE publication typeA1 Journal article-refereed

Keywords

  • Antiproliferation effect
  • Benzazulene
  • Biocompatibility
  • Cellular uptake
  • Drug loading
  • Lignin nanoparticles

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    Figueiredo, P., Lintinen, K., Kiriazis, A., Hynninen, V., Liu, Z., Bauleth-Ramos, T., Rahikkala, A., Correia, A., Kohout, T., Sarmento, B., Yli-Kauhaluoma, J., Hirvonen, J., Ikkala, O., Kostiainen, M. A., & Santos, H. A. (2017). In vitro evaluation of biodegradable lignin-based nanoparticles for drug delivery and enhanced antiproliferation effect in cancer cells. Biomaterials, 121, 97-108. https://doi.org/10.1016/j.biomaterials.2016.12.034