Functionalized Pt(II) and Ir(III) NIR emitters and their covalent conjugates with polymer-based nanocarriers.

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, N^N - 4-Oxo-4-((1-(pyridin-2-yl)-1H-1,2,3-triazol-4-yl)methoxy)butanoic acid N-hydroxysuccinimide ether). Their photophysics was carefully studied and analyzed using TD DFT 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 inverse their charge from positive to negative value. The MPs size determined with DLS varies considerably from 720 to 1480 nm, but NPs diameter falls in a rather narrow range, 210-230 nm. The species with poly(L-lysine) shell display high positive (> 30 mV) zeta-potential that make them essentially stable in aqueous media. Inversion of the surface charge to negative value with the heparin cover did not deteriorate the species stability. The iridium and platinum containing particles display emission, the spectral patterns of which were essentially similar to those of unconjugated complexes that indicate retaining 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 towards 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-potential were more readily up-taken by the cells than those with negative one.