4 research outputs found
Type 1 Phototherapeutic Agents. 2. Cancer Cell Viability and ESR Studies of Tricyclic Diarylamines
Type 1 phototherapeutic agents based on diarylamines
were assessed
for free radical generation and evaluated in vitro for cell death
efficacy in the U937 leukemia cancer cell line. All of the compounds
were found to produce copious free radicals upon photoexcitation with
UV-A and/or UV–B light, as determined by electron spin resonance
(ESR) spectroscopy. Among the diarylamines, the most potent compounds
were acridan (<b>4</b>) and 9-phenylacridan (<b>5</b>),
with IC<sub>50</sub> values of 0.68 μM and 0.17 μM, respectively
Paclitaxel-Loaded SCK Nanoparticles: An Investigation of Loading Capacity and Cell Killing Abilities <i>in Vitro</i>
Block copolymer nanoparticles having two different hydrodynamic
diameters (120 nm vs 50 nm) and core diameters (60 nm vs 20 nm) with
variable paclitaxel loading (5 to 20 wt % with respect to polymer
weight, 4.4 μg/mL to 21.7 μg/mL paclitaxel concentrations
in ultrapure water) were prepared for their <i>in vitro</i> cytotoxicity evaluation. Empty nanoparticles did not show any inherent
cytotoxicity even at their highest concentration, whereas paclitaxel-loaded
nanoparticles resulted in IC<sub>50</sub> values that were better
than free paclitaxel at 2 h (0.021 μM vs 0.046 μM) incubation
periods, and approximately equal to free paclitaxel at 72 h (0.004
μM vs 0.003 μM) continuous incubation. Confocal fluorescence
microscopy images demonstrated that the drug-loaded nanoparticles
internalized into KB cells within 2 h and released their payload,
resulting in cytotoxicity as evident from the fragmented nuclei present.
Functionalization of the nanoparticle surfaces with polyÂ(ethylene
oxide) (2 kDa PEO, 5 PEO per block copolymer chain) did not affect
the loading of paclitaxel or cell kill ability. No free paclitaxel
was found in these nanoparticle formulations indicated by analytical
assays
<i>In Vitro</i> Efficacy of Paclitaxel-Loaded Dual-Responsive Shell Cross-Linked Polymer Nanoparticles Having Orthogonally Degradable Disulfide Cross-Linked Corona and Polyester Core Domains
Paclitaxel-loaded
shell cross-linked polymeric nanoparticles
having an enzymatically and hydrolytically degradable polyÂ(lactic
acid) core and a glutathione-responsive disulfide cross-linked polyÂ(oligoethylene
glycol)-containing corona were constructed in aqueous solution and
investigated for their stimuli-responsive release of the embedded
therapeutics and <i>in vitro</i> cytotoxicity. Paclitaxel
release from the nanoparticles in PBS buffer was accelerated in the
presence of glutathione at both pH 5.5 and pH 7.4, reaching <i>ca</i>. 65% cumulative drug release after 8 d, whereas only <i>ca</i>. 50% and 35% extents of release were observed in the
absence of glutathione at pH 5.5 and pH 7.4, respectively. Enzyme-catalyzed
hydrolysis of the nanoparticle core resulted in the degradation of <i>ca</i>. 30% of the polyÂ(lactic acid) core to lactic acid within
12 h, with coincidently triggered paclitaxel release of <i>ca</i>. 37%, as opposed to only <i>ca</i>. 17% release from the
uncatalyzed nanoparticles at pH 7.4. While empty nanoparticles did
not show any inherent cytotoxicity at the highest tested concentrations,
paclitaxel-loaded nanoparticles showed IC<sub>50</sub> values that
were similar to those of free paclitaxel at 72 h incubation with KB
cells and were more efficacious at <i>ca</i>. 3-fold lower
IC<sub>50</sub> value (0.031 μM vs 0.085 μM) at 2 h of
incubation. Against human ovarian adenocarcinoma cells, the paclitaxel-loaded
nanoparticles exhibited a remarkable <i>ca</i>. 11-fold
lower IC<sub>50</sub> than a Taxol-mimicking formulation (0.0007 μM
vs 0.008 μM) at 72 h of incubation. These tunable dual-responsive
degradable nanoparticles show great promise for delivery of paclitaxel
to tumor tissues, given their superior <i>in vitro</i> efficacies
compared to that of free paclitaxel and Taxol-mimicking formulations
<i>In Vitro</i> Efficacy of Paclitaxel-Loaded Dual-Responsive Shell Cross-Linked Polymer Nanoparticles Having Orthogonally Degradable Disulfide Cross-Linked Corona and Polyester Core Domains
Paclitaxel-loaded
shell cross-linked polymeric nanoparticles
having an enzymatically and hydrolytically degradable polyÂ(lactic
acid) core and a glutathione-responsive disulfide cross-linked polyÂ(oligoethylene
glycol)-containing corona were constructed in aqueous solution and
investigated for their stimuli-responsive release of the embedded
therapeutics and <i>in vitro</i> cytotoxicity. Paclitaxel
release from the nanoparticles in PBS buffer was accelerated in the
presence of glutathione at both pH 5.5 and pH 7.4, reaching <i>ca</i>. 65% cumulative drug release after 8 d, whereas only <i>ca</i>. 50% and 35% extents of release were observed in the
absence of glutathione at pH 5.5 and pH 7.4, respectively. Enzyme-catalyzed
hydrolysis of the nanoparticle core resulted in the degradation of <i>ca</i>. 30% of the polyÂ(lactic acid) core to lactic acid within
12 h, with coincidently triggered paclitaxel release of <i>ca</i>. 37%, as opposed to only <i>ca</i>. 17% release from the
uncatalyzed nanoparticles at pH 7.4. While empty nanoparticles did
not show any inherent cytotoxicity at the highest tested concentrations,
paclitaxel-loaded nanoparticles showed IC<sub>50</sub> values that
were similar to those of free paclitaxel at 72 h incubation with KB
cells and were more efficacious at <i>ca</i>. 3-fold lower
IC<sub>50</sub> value (0.031 μM vs 0.085 μM) at 2 h of
incubation. Against human ovarian adenocarcinoma cells, the paclitaxel-loaded
nanoparticles exhibited a remarkable <i>ca</i>. 11-fold
lower IC<sub>50</sub> than a Taxol-mimicking formulation (0.0007 μM
vs 0.008 μM) at 72 h of incubation. These tunable dual-responsive
degradable nanoparticles show great promise for delivery of paclitaxel
to tumor tissues, given their superior <i>in vitro</i> efficacies
compared to that of free paclitaxel and Taxol-mimicking formulations