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

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• 作者：Patrí ; cia Figueiredo^a ; ^{patricia.figueiredo@helsinki.fi} ; Kalle Lintinen^b ; Alexandros Kiriazis^a ; Ville Hynninen^c ; Zehua Liu^a ; Tomá ; s Bauleth-Ramos^a ; ^d ; ^e ; ^f ; Antti Rahikkala^a ; Alexandra Correia^a ; Tomá ; &scaron ; Kohout^g ; Bruno Sarmento^d ; ^e ; ^f ; Jari Yli-Kauhaluoma^a ; Jouni Hirvonen^a ; Olli Ikkala^c ; Mauri A. Kostiainen^b ; Hé ; lder A. Santos^a ; ^{helder.santos@helsinki.fi}
• 关键词：Lignin nanoparticles ; Biocompatibility ; Cellular uptake ; Drug loading ; Benzazulene ; Antiproliferation effect
• 刊名：Biomaterials
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：121
• 期：Complete
• 页码：97-108
• 全文大小：2201 K
• 卷排序：121

文摘

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.