2 research outputs found
Coordination to Imidazole Ring Switches on Phosphorescence of Platinum Cyclometalated Complexes: The Route to Selective Labeling of Peptides and Proteins via Histidine Residues
In this study, we have shown that
substitution of chloride ligand
for imidazole (Im) ring in the cyclometalated platinum complex Pt(phpy)(PPh<sub>3</sub>)Cl (<b>1</b>; phpy, 2-phenylpyridine; PPh<sub>3</sub>, triphenylphosphine), which is nonemissive in solution, switches
on phosphorescence of the resulting compound. Crystallographic and
nuclear magnetic resonance (NMR) spectroscopic studies of the substitution
product showed that the luminescence ignition is a result of Im coordination
to give the [Pt(phpy)(Im)(PPh<sub>3</sub>)]Cl complex. The other imidazole-containing
biomolecules, such as histidine and histidine-containing peptides
and proteins, also trigger luminescence of the substitution products.
The complex <b>1</b> proved to be highly selective toward the
imidazole ring coordination that allows site-specific labeling of
peptides and proteins with <b>1</b> using the route, which is
orthogonal to the common bioconjugation schemes via lysine, aspartic
and glutamic acids, or cysteine and does not require any preliminary
modification of a biomolecule. The utility of this approach was demonstrated
on (i) site-specific modification of the ubiquitin, a small protein
that contains only one His residue in its sequence, and (ii) preparation
of nonaggregated HSA-based Pt phosphorescent probe. The latter particles
easily internalize into the live HeLa cells and display a high potential
for live-cell phosphorescence lifetime imaging (PLIM) as well as for
advanced correlation PLIM and FLIM experiments
VEGF- and VEGFR2-Targeted Liposomes for Cisplatin Delivery to Glioma Cells
Targeted
delivery of anticancer drugs to brain tumors, especially
glioblastoma multiforme, which is the most frequent and aggressive
type, is one of the important objectives in nanomedicine. Vascular
endothelial growth factor (VEGF) and its receptor type II (VEGFR2)
are promising targets because they are overexpressed by not only core
tumor cells but also by migrated glioma cells, which are responsible
for resistance and rapid progression of brain tumors. The purpose
of the present study was to develop the liposomal drug delivery system
combining enhanced loading capacity of cisplatin and high binding
affinity to glioma cells. This was achieved by using of highly soluble
cisplatin analogue, <i>cis</i>-diamminedinitratoplatinum(II),
and antibodies against the native form of VEGF or VEGFR2 conjugated
to liposome surface. The developed drug delivery system revealed sustained
drug release profile, high affinity to antigens, and increased uptake
by glioma C6 and U-87 MG cells. Pharmacokinetic study on glioma C6-bearing
rats revealed prolonged blood circulation time of the liposomal formulation.
The above features enabled the present drug delivery system to overcome
both poor pharmacokinetics typical for platinum formulations and low
loading capacity typical for conventional liposomal cisplatin formulations