TY - JOUR

T1 - Functionalized Pt(II) and Ir(III) NIR Emitters and Their Covalent Conjugates with Polymer-Based Nanocarriers

AU - Kritchenkov, Ilya S.

AU - Zhukovsky, Daniil D.

AU - Mohamed, Abdelrahman

AU - Korzhikov-Vlakh, Viktor A.

AU - Tennikova, Tatiana B.

AU - Lavrentieva, Antonina

AU - Scheper, Thomas

AU - Pavlovskiy, Vladimir V.

AU - Porsev, Vitaly V.

AU - Evarestov, Robert A.

AU - Tunik, Sergey P.

N1 - Funding information: Financial support was provided by Government of Russian Federation (Megagrant No. 14.W03.31.0025, “Biohybrid technologies for modern medicine”). The study of the effects of polyester NPs and MPs modification by polyelectrolytes (PLys and Hep) on particles’ stability and their cellular uptake was financially supported by RSF 19-73-10045. The NMR, photophysical, and analytical measurements were performed using the following core facilities at St. Petersburg State University Research Park: Centre for Magnetic Resonance and Centre for Chemical Analysis and Materials Research.

PY - 2020/5/20

Y1 - 2020/5/20

N2 - Two NIR-emitting platinum [Pt(N^N^C)(phosphine)] and iridium [Ir(N^C)2(N^N)]+ complexes containing reactive succinimide groups were synthesized and characterized with spectroscopic methods (N^N^C, 1-phenyl-3-(pyridin-2-yl)benzo[4,5]imidazo[1,2-a]pyrazine, N^C, 6-(2-benzothienyl)phenanthridine, phosphine-3-(diphenylphosphaneyl)propanoic acid N-hydroxysuccinimide ether, and N^N, 4-oxo-4-((1-(pyridin-2-yl)-1H-1,2,3-triazol-4-yl)methoxy)butanoic acid N-hydroxysuccinimide ether). Their photophysics were carefully studied and analyzed using time-dependent density functional theory calculations. These complexes were used to prepare luminescent micro- and nanoparticles with the "core-shell" morphology, where the core consisted of biodegradable polymers of different hydrophobicity, namely, poly(d,l-lactic acid), poly(ε-caprolactone), and poly(ω-pentadecalactone), whereas the shell was formed by covalent conjugation with poly(l-lysine) covalently labeled with the platinum and iridium emitters. The surface of the species was further modified with heparin to reverse their charge from positive to negative values. The microparticles' size determined with dynamic laser scanning varies considerably from 720 to 1480 nm, but the nanoparticles' diameter falls in a rather narrow range, 210-230 nm. The species with a poly(l-lysine) shell display a high positive (>30 mV) zeta-potential that makes them essentially stable in aqueous media. Inversion of the surface charge to a negative value with the heparin cover did not deteriorate the species' stability. The iridium- and platinum-containing particles displayed emissions the spectral patterns of which were essentially similar to those of unconjugated complexes, which indicate retention of the chromophore nature upon binding to the polymer and further immobilization onto polyester micro- and nanoparticles for drug delivery. The obtained particles were tested to determine their ability to penetrate into different cells types: cancer cells, stem cells, and fibroblasts. It was found that all types of particles could effectively penetrate into all cells types under investigation. Nanoparticles were shown to penetrate into the cells more effectively than microparticles. However, positively charged nanoparticles covered with poly(l-lysine) seem to interact with negatively charged proteins in the medium and enter the inner part of the cells less effectively than nanoparticles covered with poly(l-lysine)/heparin. In the case of microparticles, the species with positive zeta-potentials were more readily up-taken by the cells than those with negative values.

AB - Two NIR-emitting platinum [Pt(N^N^C)(phosphine)] and iridium [Ir(N^C)2(N^N)]+ complexes containing reactive succinimide groups were synthesized and characterized with spectroscopic methods (N^N^C, 1-phenyl-3-(pyridin-2-yl)benzo[4,5]imidazo[1,2-a]pyrazine, N^C, 6-(2-benzothienyl)phenanthridine, phosphine-3-(diphenylphosphaneyl)propanoic acid N-hydroxysuccinimide ether, and N^N, 4-oxo-4-((1-(pyridin-2-yl)-1H-1,2,3-triazol-4-yl)methoxy)butanoic acid N-hydroxysuccinimide ether). Their photophysics were carefully studied and analyzed using time-dependent density functional theory calculations. These complexes were used to prepare luminescent micro- and nanoparticles with the "core-shell" morphology, where the core consisted of biodegradable polymers of different hydrophobicity, namely, poly(d,l-lactic acid), poly(ε-caprolactone), and poly(ω-pentadecalactone), whereas the shell was formed by covalent conjugation with poly(l-lysine) covalently labeled with the platinum and iridium emitters. The surface of the species was further modified with heparin to reverse their charge from positive to negative values. The microparticles' size determined with dynamic laser scanning varies considerably from 720 to 1480 nm, but the nanoparticles' diameter falls in a rather narrow range, 210-230 nm. The species with a poly(l-lysine) shell display a high positive (>30 mV) zeta-potential that makes them essentially stable in aqueous media. Inversion of the surface charge to a negative value with the heparin cover did not deteriorate the species' stability. The iridium- and platinum-containing particles displayed emissions the spectral patterns of which were essentially similar to those of unconjugated complexes, which indicate retention of the chromophore nature upon binding to the polymer and further immobilization onto polyester micro- and nanoparticles for drug delivery. The obtained particles were tested to determine their ability to penetrate into different cells types: cancer cells, stem cells, and fibroblasts. It was found that all types of particles could effectively penetrate into all cells types under investigation. Nanoparticles were shown to penetrate into the cells more effectively than microparticles. However, positively charged nanoparticles covered with poly(l-lysine) seem to interact with negatively charged proteins in the medium and enter the inner part of the cells less effectively than nanoparticles covered with poly(l-lysine)/heparin. In the case of microparticles, the species with positive zeta-potentials were more readily up-taken by the cells than those with negative values.

UR - http://www.scopus.com/inward/record.url?scp=85085265368&partnerID=8YFLogxK

U2 - 10.1021/acs.bioconjchem.0c00020

DO - 10.1021/acs.bioconjchem.0c00020

M3 - Article

C2 - 32223218

AN - SCOPUS:85085265368

VL - 31

SP - 1327

EP - 1343

JO - Bioconjugate chemistry

JF - Bioconjugate chemistry

SN - 1043-1802

IS - 5

ER -