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.

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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.

access funding enabled and organized by ProjektDEAL.

The dysfunctional metabolism of glucose in cancer cells represents a new avenue for cancer targeting based on sugar-derived carriers. Here, glucose-derived carbon spheres (CS) were prepared through a simple hydrothermal method, yielding highly homogenous spherical particles that exhibited excellent stability in aqueous solution. The abundant presence of surface hydroxyl functionalities was used for a subsequent condensation of an amino silane that was the basis for further covalent coupling strategies. CS were modified with a cyclooctyne derivative providing a highly selective binding site for copper-free click reactions. Moreover, the surface modification of CS with a dye-label allowed for their intracellular detection revealing a preferential uptake of CS, compared to silica particles, in tumor cells. These results thus demonstrate the highly promising potential of glucose-derived particles for tumor targeting applications and their efficient surface modification.

Two new Drug Delivery Systems (DDS) cyclo[DKP‐isoDGR]‐PEG‐4‐Val‐Ala‐PTX (2) and cyclo[DKP‐isoDGR]‐PEG‐4‐sC18‐Val‐Ala‐PTX (3), containing the cyclo[DKP‐isoDGR] integrin ligand and the cytotoxic agent Paclitaxel (PTX), were synthesized to investigate the influence of a PEG‐4 chain and of the sC18 cell‐penetrating peptide (CPP) on the cellular uptake and the cytotoxicity of the constructs. A “double click‐reaction strategy” was planned, to realize the connection of cyclo[DKP‐isoDGR] and PTX to the CPP moiety. Anti‐proliferative bioassays were performed on the αVβ3‐positive U87 human glioblastoma cell line using a short contact time (15 min) followed by draining, washing of the cells, and re‐incubation for 72 h. Compound 3 was significantly more potent (IC50=27.6 μM) than compound 2 (IC50>100 μM), and showed a reduced potency loss with respect to PTX (IC50=71 nM).