Carboxyl-modified Nanoparticles Research Articles

Nanoparticle-Membrane Interactions Studied with Lipid Bilayer Arrays

Nanoparticles (NPs) have been explored for use in biomedical applications including gene and drug delivery, and recent studies have indicated that they are also cytotoxic and have significant interaction with lipid bilayer membranes. An understanding of the interactions between NPs and the cell membrane systems will help aid the design of NPs for beneficial applications and evaluate the cytotoxicity of environmental NPs. To study these interactions, we measured amine- and carboxyl-modified polystyrene NPs in arrays of 24-32 artificial lipid bilayers. The throughput possible with simultaneous electrical measurement of the bilayer arrays enabled study of NP/bilayer interactions while varying lipid composition, ionic strength, pH, voltage, and particle type. Our studies showed that amine-modified NPs interacted with bilayers whereas carboxyl-modified NPs did not. The interaction of the amine-modified NPs could be altered by changing the charge density on the bilayers, the ionic strength and pH.

Polystyrene nanoparticles affecting blood coagulation

The association of nanoparticles (NPs) with blood coagulation proteins may influence the natural balance between pro- and anticoagulant pathways. We investigated whether polystyrene NPs, when added to human plasma, affected the generation of thrombin in plasma. Amine-modified NPs were found to decrease the thrombin formation due to binding of factors VII and IX to the NPs, which resulted in depletion of the respective protein in solution. In contrast, carboxyl-modified NPs were able to act as a surface for activation of the intrinsic pathway of blood coagulation in plasma. These results highlight the influence of NPs on a biologically important pathway. From the Clinical EditorWith the expected introduction of several nanoparticle-based therapeutic and diagnostic methods in the near future, their impact on basic homeostasis and obligatory biological processes needs to be carefully and accurately studied. In this study, the effects of polystyrene NP-s was investigated on blood coagulation pathways, and critically important biomodulatory effects were found.

Abstract 5441: A rapid homogeneous immunoassay for the therapeutic drug management of imatinib in plasma using a novel selective monoclonal antibody

Abstract Objective: Imatinib is a potent and selective inhibitor of the Bcr-Abl and KIT protein tyrosine kinases. It is widely used for treatment of Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) and KIT-positive gastrointestinal stromal tumor (GIST). Studies have shown a significant inter-patient variability in imatinib trough concentrations up to 16 fold and a correlation between systemic exposure of the drug and clinical outcome. The current physical methods for measuring imatinib require specially trained personnel, larger sample sizes, are expensive, time consuming and not amenable for widespread use. The objective of this study is to develop an automated immunoassay that provides a rapid, simple and inexpensive method to routinely measure exposure of imatinib in patients undergoing chemotherapy. Methods: A library containing five novel and highly selective antibodies to imatinib were covalently linked to carboxyl-modified nanoparticles to develop a prototype automated homogenous assay for use on the Beckman Coulter AU®400 clinical analyzer which uses a two reagent system and 2 uL of plasma to quantitate imatinib. The degree of aggregation of nanoparticles, inversely proportional to the concentration of imatinib in a sample, was monitored at 600 nm. Total imprecision and linearity of the assay were evaluated by testing normal human plasma (NHP) pools spiked with different levels of imatinib. The background of the assay was also determined by measuring >100 NHP blank samples. Immunoassay selectivity was characterized by testing metabolites including N-desmethylimatinib and other structure-related compounds of imatinib for cross-reactivity at relevant physiological concentrations. Results: With a quantitative range from 100 to 4,000 ng/mL and instrument auto-dilution, plasma samples with imatinib concentrations up to 10,000 ng/mL could be determined using this assay. Time-to-first result was 11 minutes and 400 samples per hour could be measured using a stored calibration curve. The total imprecision of NHP pools spiked with imatinib at four concentrations across the assay range was <10% CV and the assay was linear from 100 to 4,000 ng/mL. The background of the assay was <50 ng/mL. The assay cross-reactivities to N-desmethylimatinib and other cross-reactants were determined to have insignificant impact on the quantitation of imatinib. Conclusion: This immunoassay is suitable for determining imatinib concentrations in plasma with the advantages of speed, small sample size, no sample pretreatment and application on automated instrumentation, providing a tool for optimization of imatinib plasma trough levels with pharmacokinetic-guided dosing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5441. doi:10.1158/1538-7445.AM2011-5441

Experimental study on the surface modification ofY2O3:Tm3+/Yb3+ nanoparticles to enhance upconversion fluorescence and weaken aggregation

In order to improve the solubility of doped nanoparticles in solutions,Y2O3:Tm3+/Yb3+ nanoparticles were synthesized using the Pechini-type sol–gel method, and their surfaces weremodified with amino or carboxylic functional groups using ligand-capped and ligand-exchangingmethods. The nanoparticles with modified surfaces were characterized by transmission electronmicroscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy and zeta potential(ζ), and their photoluminescence was studied by fluorescence spectrophotometry. The resultsindicate that the upconversion fluorescence of amine- and carboxyl-modified nanoparticles wasenhanced after the surfaces of nanoparticles were modified. Compared to the upconversionfluorescence intensity of non-modified nanoparticles, the upconversion fluorescence intensitiesof amine- and carboxyl-modified nanoparticles were enhanced by 9.4 and 1.4 times,respectively. These results are attributed to the formation of the chemical bonds betweenY2O3:Tm3+/Yb3+ core andnon-crystalline SiO2 shell via Y–O–Si bridges, which activate the ‘dormant’Tm3+/Yb3+ ions on the surfaces of nanoparticles. The results of the solubility investigations foramine- and carboxyl-modified nanoparticles indicate that severe aggregation can beweakened by adhering amino or carboxylic functional groups to the surfaces ofnanoparticles. It is therefore concluded that the good hydrophilicity resulting from activefunctional groups in solutions and more intense upconversion fluorescence enable the dopedcore–shell nanoparticles to have great potential to be used as fluorescence biolabels in thefuture.

Surface Modification of ZrO2:Er3+ Nanoparticles to Attenuate Aggregation and Enhance Upconversion Fluorescence

ZrO2:Er3+ nanoparticles are synthesized and further modified via a ligand-capped/ligand-exchanging method with TEOS, APTES, and SA. Antiaggregation investigations using TEM and FT-IR indicate that severe aggregation can be reduced by adhering ammonic or carboxylic functional groups to the nanoparticle surfaces. The upconversion fluorescence spectra of nonmodified and the modified nanoparticles with the same peak splitting and positions show that local crystalline environments in which the Er3+ ions are embedded are identical before and after modifying the surfaces. The remarkable upconversion fluorescence enhancements of 4.7 and 1.5 times for amine- and carboxyl-modified nanoparticles are observed under the same excitation power densities, respectively. An enhancement mechanism of upconversion luminescence, in which an asymmetric association crystalline field from both the degenerated crystalline field of the host interface and a complementary crystal field of the SiO2 shell can make the ‘dormant' rare earth ions on nanoparticle surfaces be activated, is presented. In addition, the improved spontaneous emission rate of Er3+ ions due to the enhanced local classical density of states and organic ligands with high vibrational energy on the nanoparticle surfaces are also considered. Thus, intense upconversion fluorescence and hydrophilicity via ammonic or carboxylic functional groups will provide the doped core−shell nanoparticles great potential as biolabels in the future.