TY - JOUR

T1 - Design and synthesis of lipid-mimetic cationic iridium complexes and their liposomal formulation for

T2 - In vitro and in vivo application in luminescent bioimaging

AU - Shakirova, Julia R.

AU - Sadeghi, Amir

AU - Koblova, Alla A.

AU - Chelushkin, Pavel S.

AU - Toropainen, Elisa

AU - Tavakoli, Shirin

AU - Kontturi, Leena Stiina

AU - Lajunen, Tatu

AU - Tunik, Sergey P.

AU - Urtti, Arto

PY - 2020/4/8

Y1 - 2020/4/8

N2 - Two iridium [Ir(N^C)2(N^N)]+ complexes with the diimine N^N ligand containing a long polymethylene hydrophobic chain were synthesized and characterized by using NMR and ESI mass-spectrometry: N^N-2-(1-hexadecyl-1H-imidazol-2-yl)pyridine, N^C-methyl-2-phenylquinoline-4-carboxylate (Ir1) and 2-phenylquinoline-4-carboxylic acid (Ir2). These complexes were used to prepare the luminescent PEGylated DPPC liposomes (DPPC/DSPE-PEG2000/Ir-complex = 95/4.5/1 mol%) using a thin film hydration method. The narrowly dispersed liposomes had diameters of about 110 nm. The photophysics of the complexes and labeled liposomes were carefully studied. Ir1 and Ir2 give red emission (λem = 667 and 605 nm) with a lifetime in the microsecond domain and quantum yields of 4.8% and 10.0% in degassed solution. Incorporation of the complexes into the liposome lipid bilayer results in shielding of the emitters from interaction with molecular oxygen and partial suppression of excited state nonradiative relaxation due to the effect of the relatively rigid bilayer matrix. Delivery of labeled liposomes to the cultured ARPE-19 cells demonstrated the usefulness of Ir1 and Ir2 in cellular imaging. Labeled liposomes were then injected intravitreally into rat eyes and imaged successfully with optical coherence tomography and funduscopy. In conclusion, iridium complexes enabled the successful labeling and imaging of liposomes in cells and animals.

AB - Two iridium [Ir(N^C)2(N^N)]+ complexes with the diimine N^N ligand containing a long polymethylene hydrophobic chain were synthesized and characterized by using NMR and ESI mass-spectrometry: N^N-2-(1-hexadecyl-1H-imidazol-2-yl)pyridine, N^C-methyl-2-phenylquinoline-4-carboxylate (Ir1) and 2-phenylquinoline-4-carboxylic acid (Ir2). These complexes were used to prepare the luminescent PEGylated DPPC liposomes (DPPC/DSPE-PEG2000/Ir-complex = 95/4.5/1 mol%) using a thin film hydration method. The narrowly dispersed liposomes had diameters of about 110 nm. The photophysics of the complexes and labeled liposomes were carefully studied. Ir1 and Ir2 give red emission (λem = 667 and 605 nm) with a lifetime in the microsecond domain and quantum yields of 4.8% and 10.0% in degassed solution. Incorporation of the complexes into the liposome lipid bilayer results in shielding of the emitters from interaction with molecular oxygen and partial suppression of excited state nonradiative relaxation due to the effect of the relatively rigid bilayer matrix. Delivery of labeled liposomes to the cultured ARPE-19 cells demonstrated the usefulness of Ir1 and Ir2 in cellular imaging. Labeled liposomes were then injected intravitreally into rat eyes and imaged successfully with optical coherence tomography and funduscopy. In conclusion, iridium complexes enabled the successful labeling and imaging of liposomes in cells and animals.

KW - OPTICAL COHERENCE TOMOGRAPHY

KW - DRUG-DELIVERY

KW - PHOTOPHYSICAL PROPERTIES

KW - LOADED LIPOSOMES

KW - FLUORESCENT

KW - LIGANDS

KW - PEG

UR - http://www.scopus.com/inward/record.url?scp=85083466894&partnerID=8YFLogxK

U2 - 10.1039/d0ra01114b

DO - 10.1039/d0ra01114b

M3 - Article

AN - SCOPUS:85083466894

VL - 10

SP - 14431

EP - 14440

JO - RSC Advances

JF - RSC Advances

SN - 2046-2069

IS - 24

ER -