In the framework
of our attempts to develop cyclometalated Pt(II)
complexes toward bifunctional targeting inhibitors or agents for photodynamic
therapy, diagnostics, and bioimaging, a series of bis-cyclometalated
Pt(II) complexes [Pt(CNC)(L)] (L = DMSO, MeCN) containing various
(CNC)2– ligands based on 2,6-diphenylpyridine were
synthesized and characterized analytically and spectroscopically,
focusing on their electrochemical, luminescence, and antiproliferative
properties. Electrochemical experiments and UV–vis absorption
spectroscopy suggest ligand-centered LUMOs and metal-centered HOMOs
in line with DFT calculations. Extension of the ancillary phenyl to
naphthyl cores and a central 4-phenylpyridine group instead of pyridine
results in bathochromic shifts of the long-wavelength absorption bands
ranging from 420 to 440 nm, with the latter shift being more pronounced.
The complexes of the fused CNC heterocyclic systems dba (H2dba = dibenzo[c,h]acridine), db(ph)a
(H2db(ph)a = 7-phenyldibenzo[c,h]acridine), and bzqph (HbzqphH = 2-phenylbenzo[h]quinoline) absorb far more red-shifted in the range 500–530
nm. All complexes show reversible first electrochemical reductions
and irreversible oxidations with an electrochemical gap of about 3
V, roughly in line with the absorption energies. While the 2,6-diphenylpyridine
complexes [Pt(CNC)(DMSO)] show no luminescence at ambient temperature
in solution, the fused dba, db(ph)a, and bzqph derivatives are efficient
triplet emitters at ambient temperature with emission wavelengths
in the region 575–600 nm and quantum yields ranging from 7
to 23%. Vibrationally resolved emission spectra calculated in the
framework of DFT faithfully reproduce the experimental data. TD-DFT
calculations at the excited-state T1 geometry reveal intraligand
π–π*/MLCT character of the emission for all three
investigated complexes. Antiproliferative tests on selected complexes
gave very different toxicities, ranging from lower than 1 μM
to virtually nontoxic. The data allowed drawing some structure–activity
relationships (SAR), even though variations in solubility could also
significantly account for the different toxicities.
The capability of cell-penetrating peptides (CPPs) to enable translocation of cargos across biological barriers shows promising pharmaceutical potential for the transport of drug molecules, as well as nanomaterials, into cells.
MicroRNAs (miRNAs) are small non-coding nucleotides playing a crucial role in posttranscriptional expression and regulation of target genes in nearly all kinds of cells. In this study, we demonstrate a reliable and efficient capture and purification of miRNAs and intracellular proteins using magnetic nanoparticles functionalized with antisense oligonucleotides. For this purpose, a tumor suppressor miRNA (miR-198), deregulated in several human cancer types, was chosen as the model oligonucleotide. Magnetite nanoparticles carrying the complementary sequence of miR-198 (miR-198 antisense) on their surface were delivered into cells and subsequently used for the extracellular transport of miRNA and proteins. The successful capture of miR-198 was demonstrated by isolating RNA from magnetic nanoparticles followed by real-time PCR quantification. Our experimental data showed that antisense-coated particles captured 5-fold higher amounts of miR-198 when compared to the control nanoparticles. Moreover, several proteins that could play a significant role in miR-198 biogenesis were found attached to miR-198 conjugated nanoparticles and analyzed by mass spectrometry. Our findings demonstrate that a purpose-driven vectorization of magnetic nanobeads with target-specific recognition ligands is highly efficient in selectively transporting miRNA and disease-relevant proteins out of cells and could become a reliable and useful tool for future diagnostic, therapeutic and analytical applications.
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