title: In vitro evaluation of biodegradable lignin-based nanoparticles for drug delivery and enhanced antiproliferation effect in cancer cells.
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.
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland. Electronic address: patricia.figueiredo@helsinki.fi.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Figueiredo
authors.affiliation: Biohybrid Materials, Department of Biotechnology and Chemical Technology, Aalto University, FI-00076, Espoo, Finland.
authors.forename: Kalle
authors.initials: K
authors.lastname: Lintinen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Kiriazis
authors.affiliation: Molecular Materials, Department of Applied Physics, Aalto University School of Science, FI-00076, Espoo, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Hynninen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
authors.forename: Zehua
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland; Instituto de Investigação e Inovação em Saúde (I3S), University of Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal; Instituto de Engenharia Biomédica (INEB), University of Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal; Instituto Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Rua Jorge Viterbo 228, 4150-180, Porto, Portugal.
authors.forename: Tomás
authors.initials: T
authors.lastname: Bauleth-Ramos
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Rahikkala
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Correia
authors.affiliation: Department of Physics, University of Helsinki, FI-00560, Helsinki, Finland.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Kohout
authors.affiliation: Instituto de Investigação e Inovação em Saúde (I3S), University of Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal; Instituto de Engenharia Biomédica (INEB), University of Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal; Instituto Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Rua Jorge Viterbo 228, 4150-180, Porto, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Yli-Kauhaluoma
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.affiliation: Molecular Materials, Department of Applied Physics, Aalto University School of Science, FI-00076, Espoo, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Ikkala
authors.affiliation: Biohybrid Materials, Department of Biotechnology and Chemical Technology, Aalto University, FI-00076, Espoo, Finland.
authors.forename: Mauri A
authors.initials: MA
authors.lastname: Kostiainen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland. Electronic address: helder.santos@helsinki.fi.
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
mesh_terms: D020341:Absorbable Implants; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D008031:Lignin / Q000008:administration & dosage / Q000737:chemistry*; D061986:MCF-7 Cells; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D053769:Nanocapsules; D008031:Lignin
keywords: Antiproliferation effect; Benzazulene; Biocompatibility; Cellular uptake; Drug loading; Lignin nanoparticles