Noninvasive detection of nanoparticle clustering by water proton NMR

Taraban, Marc B.; Truong, Huy C.; Ilavský, Ján; DePaz, Roberto A; Lobo, Brian A.; Yu, Yinan

doi:10.1088/2053-1613/aa7838

Cited by 8 publications

(9 citation statements)

References 18 publications

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“…In case of high magnetic susceptibility contrast, local magnetic field gradient is generated at the water-solute interface which accelerates spin de-coherence and results in the increase of R 2 ( 1 H 2 O). However, in the present case, we do not expect the manifestation of this third mechanism, since the magnetic susceptibility contrast between water and proteins and organic polymers is typically extremely low [ 37 ]. One also can exclude the effects of viscosity changes on the observed R 2 ( 1 H 2 O) values.…”

Section: Discussionmentioning

confidence: 86%

“…Another potential factor of w NMR sensitivity pertinent to the present study, is the formation of water compartments inside the cavities of larger agglomerates. It is well established that the diffusive exchange of compartmentalized water differs from bulk water molecules and accelerates the experimentally observed water proton relaxation [ 37 , 39 ]. Third potential mechanism affecting w NMR observations is stipulated by the difference in magnetic susceptibilities of the solute and water (magnetic susceptibility contrast) [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

“…Isothermal titration calorimetry (ITC) has been one the most important choices in studying protein-polyelectrolyte interactions and, more generally, to biomolecular recognition reactions due to repeatability, sensitivity, as well as for providing an important thermodynamic information [ 3 , 33 , 34 ]. Water proton NMR ( w NMR) is a powerful tool, which monitors the signal of water protons and its transverse relaxation rate R 2 ( 1 H 2 O) mediated by interactions with dissolved matter, was selected due to its non-invasive approach and proven sensitivity in the detection macromolecular aggregates and cluster of nanoparticulates [ 35 , 36 , 37 , 38 , 39 , 40 ]. Lastly, the results of the above analytical methods were cross-referenced with dynamic light scattering (DLS) data in an attempt to understand a potential link of the detected characteristics with physical state and dimensions of lysozyme-PCPP complexes.…”

Section: Introductionmentioning

confidence: 99%

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Supramolecular Protein-Polyelectrolyte Assembly at Near Physiological Conditions—Water Proton NMR, ITC, and DLS Study

et al. 2022

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The in vivo potency of polyphosphazene immunoadjuvants is inherently linked to the ability of these ionic macromolecules to assemble with antigenic proteins in aqueous solutions and form physiologically stable supramolecular complexes. Therefore, in-depth knowledge of interactions in this biologically relevant system is a prerequisite for a better understanding of mechanism of immunoadjuvant activity. Present study explores a self-assembly of polyphosphazene immunoadjuvant—PCPP and a model antigen—lysozyme in a physiologically relevant environment—saline solution and neutral pH. Three analytical techniques were employed to characterize reaction thermodynamics, water-solute structural organization, and supramolecular dimensions: isothermal titration calorimetry (ITC), water proton nuclear magnetic resonance (wNMR), and dynamic light scattering (DLS). The formation of lysozyme–PCPP complexes at near physiological conditions was detected by all methods and the avidity was modulated by a physical state and dimensions of the assemblies. Thermodynamic analysis revealed the dissociation constant in micromolar range and the dominance of enthalpy factor in interactions, which is in line with previously suggested model of protein charge anisotropy and small persistence length of the polymer favoring the formation of high affinity complexes. The paper reports advantageous use of wNMR method for studying protein-polymer interactions, especially for low protein-load complexes.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Supramolecular Protein-Polyelectrolyte Assembly at Near Physiological Conditions—Water Proton NMR, ITC, and DLS Study

et al. 2022

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“…Indeed, in the frames of the above suggested mechanism based on the water molecules mobility, the sensitivity of w NMR to capsid degradation could be rather high. We have previously demonstrated the response of R 2 ( 1 H 2 O) to the changes in H 2 O mobility in the case of nanoparticles clustering and the agglomeration of aluminum adjuvants in vaccine products …”

Section: Resultsmentioning

confidence: 99%

Rapid and Noninvasive Quantification of Capsid Gene Filling Level Using Water Proton Nuclear Magnetic Resonance

Taraban

Jones

2021

Anal. Chem.

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The present work reports an enabling novel technology for quantifying the gene content in adeno-associated viral capsids. The method is based on the water proton nuclear magnetic resonance (wNMR) technique. Instead of analyzing the capsid directly, it utilizes water molecules to distinguish empty and full capsids, as water interacts with them differently. The transverse relaxation rate of water protons, R 2 ( 1 H 2 O), readily distinguishes empty and full capsids and is capable of quantifying the fraction of full capsids in a mixture of full and empty ones. It involves no sample preparation and no reagents. Measurement is rapid (data collection takes 1−2 min), noninvasive (the capsid sample can stay inside the original sealed and labeled container to be used in other studies or administered to a patient), and performed using a widebore benchtop NMR instrument. The method can be readily implemented at a production plant for product release as part of product quality control.

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“…We have applied w NMR to a variety of systems, including biomaterials, 13,14 surfactants, 15 small molecules, 16 nanoparticles, 17 dendrimers, 12,18 insulin, 2,19 proteins, 15,20,21 monoclonal antibodies, 22,23 vaccine adjuvants 24,25 and vaccines. 26 We also discussed applications of w NMR in the development, 27,28 inspection, 29 and distribution 30 of drugs and vaccines.…”

Section: Introductionmentioning

confidence: 99%

Inspecting Insulin Products Using Water Proton NMR. I. Noninvasive vs Invasive Inspection

Taraban

Wang

Briggs

et al. 2021

J Diabetes Sci Technol

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Background: There is a clear need to transition from batch-level to vial/syringe/pen-level quality control of biologic drugs, such as insulin. This could be achieved only by noninvasive and quantitative inspection technologies that maintain the integrity of the drug product. Methods: Four insulin products for patient self-injection presented as prefilled pens have been noninvasively and quantitatively inspected using the water proton NMR technology. The inspection output is the water proton relaxation rate R2(1H2O), a continuous numerical variable rather than binary pass/fail. Results: Ten pens of each product were inspected. R2(1H2O) displays insignificant variation among the 10 pens of each product, suggesting good insulin content uniformity in the inspected pens. It is also shown that transferring the insulin solution out of and then back into the insulin pen caused significant change in R2(1H2O), presumably due to exposure to O2 in air. Conclusions: Water proton NMR can noninvasively and quantitatively inspect insulin pens. wNMR can confirm product content uniformity, but not absolute content. Its sensitivity to sample transferring provides a way to detect drug product tampering. This opens the possibility of inspecting every pen/vial/syringe by manufacturers and end-users.

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Noninvasive detection of nanoparticle clustering by water proton NMR

Cited by 8 publications

References 18 publications

Supramolecular Protein-Polyelectrolyte Assembly at Near Physiological Conditions—Water Proton NMR, ITC, and DLS Study

Supramolecular Protein-Polyelectrolyte Assembly at Near Physiological Conditions—Water Proton NMR, ITC, and DLS Study

Rapid and Noninvasive Quantification of Capsid Gene Filling Level Using Water Proton Nuclear Magnetic Resonance

Inspecting Insulin Products Using Water Proton NMR. I. Noninvasive vs Invasive Inspection

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