12 research outputs found
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Direct Utilization of Plasma Proteins for the In Vivo Assembly of Protein-Drug/Imaging Agent Conjugates, Nanocarriers and Coatings for Biomaterials
Patent relating to the direct utilization of plasma proteins for the in vivo assembly of protein-drug/imaging agent conjugates, nanocarriers and coatings for biomaterials
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NMR study of 2-ethylhexyllithium aggregate and 2- ethylhexyllithium/lithium 2-ethyl-1-hexoxide mixed aggregates.
A 1H, 13C, and 6Li NMR study of 2-ethylhexyllithium showed that 2- ethylhexyllithium exists solely as a hexamer in cyclopentane solution over the temperature range from 25 to -65 °C. Furthermore, 2-ethylhexyllithium and lithium 2- ethyl-1-hexoxide were shown to form mixed aggregates when the alkoxide was formed in situ by reacting 2-ethylhexyllithium with 2-ethyl-1-hexanol. A multinuclear, variable temperature NMR study of a sample with an O:Li ratio of 0.2 led to the identification of at least four such aggregates, one of which was found to be a hexamer with the composition R5(RO)Li6. Studies of samples with higher O:Li ratios, up to 0.8, showed additional mixed aggregates present. All solutions containing mixed aggregates were also shown to contain hydrocarbon soluble lithium hydride. A study of lithium 2-ethyl-1- hexoxide indicated that it aggregates in solution as well
Beyond platinum: synthesis, characterization, and in vitro toxicity of Cu(II)-releasing polymer nanoparticles for potential use as a drug delivery vector
The field of drug delivery focuses primarily on delivering small organic molecules or DNA/RNA as therapeutics and has largely ignored the potential for delivering catalytically active transition metal ions and complexes. The delivery of a variety of transition metals has potential for inducing apoptosis in targeted cells. The chief aims of this work were the development of a suitable delivery vector for a prototypical transition metal, Cu2+, and demonstration of the ability to impact cancer cell viability via exposure to such a Cu-loaded vector. Carboxylate-functionalized nanoparticles were synthesized by free radical polymerization and were subsequently loaded with Cu2+ via binding to particle-bound carboxylate functional groups. Cu loading and release were characterized via ICP MS, EDX, XPS, and elemental analysis. Results demonstrated that Cu could be loaded in high weight percent (up to 16 wt.%) and that Cu was released from the particles in a pH-dependent manner. Metal release was a function of both pH and the presence of competing ligands. The toxicity of the particles was measured in HeLa cells where reductions in cell viability greater than 95% were observed at high Cu loading. The combined pH sensitivity and significant toxicity make this copper delivery vector an excellent candidate for the targeted killing of disease cells when combined with an effective cellular targeting strategy
The Complex Role of Multivalency in Nanoparticles Targeting the Transferrin Receptor for Cancer Therapies
Transferrin receptor (TfR, CD71) has long been therapeutic target due to its over-expression on many malignant tissues. In this study, PRINT® nanoparticles were conjugated with TfR ligands for targeted drug delivery. Cylindrical poly(ethylene glycol)-based PRINT nanoparticles (diameter [d] = 200 nm, height [h] = 200 nm) labeled with transferrin receptor antibody (NP-OKT9) or human transferrin (NP-hTf), showed highly specific TfR-mediated uptake by all human tumor cell lines tested, relative to negative controls (IgG1 for OKT9 or bovine transferrin (bTf) for hTf). The targeting efficiency was dependent on particle concentration, ligand density, dosing time and cell surface receptor expression level. Interestingly, NP-OKT9 or NP-hTf showed little cytotoxicity on all solid tumor cell lines tested but were very toxic to Ramos B-cell lymphoma, whereas free OKT9 or hTf was not toxic. There was a strong correlation between TfR ligand density on particle surface and cell viability and particle uptake. NP-OKT9 and NP-hTf were internalized into acidic intracellular compartments but were not localized in EEA1 enriched early endosomes or lysosomes. Elevated caspase 3/7 activity indicates activation of apoptosis pathways upon particle treatment. Supplementation of iron suppressed the toxicity of NP-OKT9 but not NP-hTf, suggesting different mechanisms by which NP-hTf and NP-OKT9 exerts cytotoxicity on Ramos cells. Based on such an observation, the complex role of multivalency in nanoparticles is discussed. In addition, our data clearly reveal that one must be careful in making claims of “lack of toxicity” when a targeting molecule is used on nanoparticles and also raise concerns for unanticipated off-target effects when one is designing targeted chemotherapy nano-delivery agents
Formula-Driven, Size-Tunable Synthesis of PMMA Nanoparticles by Varying Surfactant Concentration
In this communication, we present a streamlined, reproducible synthetic method for the production of size-tunable poly(methyl methacrylate) (PMMA) nanoparticles (PMMANPs) and amine-functionalized block-copolymer PMMANPs (H2N-PMMANPs) by varying subcritical concentrations (i.e., below the concentration required to form micelles at 1 atm and 20 °C) of sodium dodecyl sulfate (SDS). We plotted the Z-average size data against SDS concentration, which revealed a second-order exponential decay function, expressed as A 1 e − x t 1 + A 2 e − x t 2 + y 0 . The surfactant concentration (wt./wt.%) has been selected as independent variable x. This function is valid at least for the size range of 20 nm to 97 nm (PMMANPs) and 20 nm to 133 nm (H2N-PMMANPs)
Werner Complexes Viewed Anew: Utilizing Cobalt Coordination Chemistry for ‘Traceless’ Stimuli-Responsive Bioconjugation Involving Therapeutic Nanoparticles, Protein PEGylation, and Drug-(Bio)polymer Conjugates
Self-Assembly of Linear Polymers into Phosphorescent Nanoparticles: Optimization toward Non-Cytotoxic Bioimaging and Photonic Devices
Development
of light-emitting polymers is usually hampered by inherent
drawbacks such as photobleaching, stability, and functionalization
issues. Formation of biocompatible, luminescent polymer particles
often entails hazardous chemical cross-linking processes and/or doping
with fluorophores susceptible to leaching and photobleaching. Here
we describe the formation of size-tunable phosphorescent particles
via self-assembly of chitosan and other linear polymers that bear
positive surface charges upon polyelectrolytic complexation to a polyanionic
gold(I) phosphor (AuP). The in situ self-assembly of phosphorescent
chitosan nanoparticles is enabled by AuP that performs a quadruple
role: a physical cross-linker, light emitter, sensor of polysaccharide
rings with structures akin to those of some cancer markers, and contrast
agent for electron microscopy. Size tunability in phosphorescent chitosan
particles was achieved by systematic variations in pH or reactant
concentrations. AuP exhibits “on–off” photoluminescence
(PL) switching induced by several amine-bearing linear polymers, rendering
the phosphorescent nanocomposites particularly attractive for biological
imaging and sensing applications. Finally, combination of AuP-chitosan
with a Pt-based orange-red phosphor leads to white-emitting thin films
with high color-rendering index, remarkable stability, and PL quantum
yields as high as 78% with <2% photobleaching. These properties
render such thin films useful for applications in lighting and electronic
displays