TY - JOUR
T1 - Preparation and characterization of dentin phosphophoryn-derived peptide-functionalized lignin nanoparticles for enhanced cellular uptake
AU - Figueiredo, Patricia Isabel
AU - Sipponen, Mika H.
AU - Lintinen, Kalle
AU - Rebelo Correia, Alexandra Maria
AU - Kiriazis, Alexandros
AU - Yli-Kauhaluoma, Jari Tapani
AU - Österberg, Monika
AU - George, Anne
AU - Hirvonen, Jouni Tapio
AU - Kostiainen, Mauri A.
AU - Almeida Santos, Helder
PY - 2019/6/14
Y1 - 2019/6/14
N2 - The surface modification of nanoparticles (NPs) using different ligands is a common strategy to increase NP−cell interactions. Here, dentin phosphophoryn‐derived peptide (DSS) lignin nanoparticles (LNPs) are prepared and characterized, the cellular internalization of the DSS‐functionalized LNPs (LNPs‐DSS) into three different cancer cell lines is evaluated, and their efficacy with the widely used iRGD peptide is compared. It is shown that controlled extent of carboxylation of lignin improves the stability at physiological conditions of LNPs formed upon solvent exchange. Functionalization with DSS and iRGD peptides maintains the spherical morphology and moderate polydispersity of LNPs. The LNPs exhibit good cytocompatibility when cultured with PC3‐MM2, MDA‐MB‐231, and A549 in the conventional 2D model and in the 3D cell spheroid morphology. Importantly, the 3D cell models reveal augmented internalization of peptide‐functionalized LNPs and improve antiproliferative effects when the LNPs are loaded with a cytotoxic compound. Overall, LNPs‐DSS show equal or even superior cellular internalization than the LNPs‐iRGD, suggesting that DSS can also be used to enhance the cellular uptake of NPs into different types of cells, and release different cargos intracellularly.
AB - The surface modification of nanoparticles (NPs) using different ligands is a common strategy to increase NP−cell interactions. Here, dentin phosphophoryn‐derived peptide (DSS) lignin nanoparticles (LNPs) are prepared and characterized, the cellular internalization of the DSS‐functionalized LNPs (LNPs‐DSS) into three different cancer cell lines is evaluated, and their efficacy with the widely used iRGD peptide is compared. It is shown that controlled extent of carboxylation of lignin improves the stability at physiological conditions of LNPs formed upon solvent exchange. Functionalization with DSS and iRGD peptides maintains the spherical morphology and moderate polydispersity of LNPs. The LNPs exhibit good cytocompatibility when cultured with PC3‐MM2, MDA‐MB‐231, and A549 in the conventional 2D model and in the 3D cell spheroid morphology. Importantly, the 3D cell models reveal augmented internalization of peptide‐functionalized LNPs and improve antiproliferative effects when the LNPs are loaded with a cytotoxic compound. Overall, LNPs‐DSS show equal or even superior cellular internalization than the LNPs‐iRGD, suggesting that DSS can also be used to enhance the cellular uptake of NPs into different types of cells, and release different cargos intracellularly.
KW - 3D cell culture
KW - CANCER-THERAPY
KW - DRUG-DELIVERY
KW - INHIBITION
KW - KINASES
KW - POLYMERIC NANOPARTICLES
KW - POROUS SILICON NANOPARTICLES
KW - SYSTEMS
KW - benzazulene
KW - biofunctionalization
KW - dentin phosphophoryn peptide
KW - lignin nanoparticles
KW - 116 Chemical sciences
KW - 221 Nano-technology
KW - 317 Pharmacy
U2 - 10.1002/smll.201901427
DO - 10.1002/smll.201901427
M3 - Article
VL - 15
JO - Small
JF - Small
SN - 1613-6810
IS - 24
M1 - 1901427
ER -