Oxygenation is one of the most important physiological parameters of biological systems. Low oxygen concentration (hypoxia) is associated with various pathophysiological processes in different organs. Hypoxia is of special importance in tumor therapy, causing poor response to treatment. Triaryl methyl (TAM) derivative radicals are commonly used in electron paramagnetic resonance (EPR) as sensors for quantitative spatial tissue oxygen mapping. They are also known as magnetic resonance imaging (MRI) contrast agents and fluorescence imaging compounds. We report the properties of the TAM radical tris(2,3,5,6-tetrachloro-4-carboxy-phenyl)methyl, (PTMTC), a potential multimodal (EPR/fluorescence) marker. PTMTC was spectrally analyzed using EPR and characterized by estimation of its sensitivity to the oxygen in liquid environment suitable for intravenous injection (1 mM PBS, pH = 7.4). Further, fluorescent emission of the radical was measured using the same solvent and its quantum yield was estimated. An in vitro cytotoxicity examination was conducted in two cancer cell lines, HT-29 (colorectal adenocarcinoma) and FaDu (squamous cell carcinoma) and followed by uptake studies. The stability of the radical in different solutions (PBS pH = 7.4, cell media used for HT-29 and FaDu cells culturing and cytotoxicity procedure, full rat blood and blood plasma) was determined. Finally, a primary toxicity test of PTMTC was carried out in mice. Results of spectral studies confirmed the multimodal properties of PTMTC. PTMTC was demonstrated to be not absorbed by cancer cells and did not interfere with luciferin-luciferase based assays. Also in vitro and in vivo tests showed that it was non-toxic and can be freely administrated till doses of 250 mg/kg BW via both i.v. and i.p. injections. This work illustrated that PTMTC is a perfect candidate for multimodal (EPR/fluorescence) contrast agent in preclinical studies.
In
continuation of previous work, we present a new promising DNA
carrier,
OO4
, a highly effective peptide-mimicking lysine-based
cationic lipid. The structural characteristics of the polynucleotide
carrier system
OO4
mixed with the commonly used co-lipid
DOPE
and the saturated phospholipid
DPPE
have
been studied in two-dimensional and three-dimensional model systems
to understand their influence on the physical–chemical properties.
The phase behavior of pure
OO4
and its mixtures with
DOPE
and
DPPE
was studied at the air–water
interface using a Langmuir film balance combined with infrared reflection-absorption
spectroscopy. In bulk, the self-assembling structures in the presence
and absence of DNA were determined by small-angle and wide-angle X-ray
scattering. The amount of adsorbed DNA to cationic lipid bilayers
was measured using a quartz crystal microbalance. The choice of the
co-lipid has an enormous influence on the structure and capability
of binding DNA.
DOPE
promotes the formation of nonlamellar
lipoplexes (cubic and hexagonal structures), whereas
DPPE
promotes the formation of lamellar lipoplexes. The correlation of
the observed structures with the transfection efficiency and serum
stability indicates that
OO4
/
DOPE
1:3 lipoplexes
with a DNA-containing cubic phase encapsulated in multilamellar structures
seem to be most promising.
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