Understanding Nanomedicine Size and Biological Response Dependency: What Is the Relevance of Previous Relationships Established on Only Batch-Mode DLS-Measured Sizes?

Oliveira, Elquio Eleamen; Barendji, Maryème; Vauthier, Christine

doi:10.1007/s11095-020-02869-x

Cited by 5 publications

(2 citation statements)

References 91 publications

(153 reference statements)

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“…5 The scattering signal from large particles or small aggregates can easily eclipse that from single molecules. 6 Biological solutions contain various proteins and other macromolecules that may induce NP aggregation, leading to a high degree of polydispersity and difficulties in assessing appropriate dosage, toxicological findings, and identifying therapeutic mechanisms of action. 7 Measurement of size and aggregation state via DLS is only an indirect readout of the NP surface properties.…”

Section: Introductionmentioning

confidence: 99%

Single-nanoparticle electrophoretic mobility determination and trapping using active-feedback 3D tracking

Johnson,

Welsher

2024

Preprint

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Nanoparticles (NP) are versatile materials with widespread applications across medicine and engineering. Despite rapid incorporation into drug delivery, therapeutics, and many more areas of research and development, there is a lack of robust characterization methods. Light scattering techniques such as dynamic light scattering (DLS) and electrophoretic light scattering (ELS) use an ensemble-averaged approach to the characterization of nanoparticle size and electrophoretic mobility (EM), leading to inaccuracies when applied to polydisperse or heterogeneous populations. To address this lack of single-nanoparticle characterization, this work applies 3D Single-Molecule Active Real-time Tracking (3D-SMART) to simultaneously determine NP size and EM on a per-particle basis. Single-nanoparticle EM is determined by using active feedback to “lock on” to a single particle and apply an oscillating electric field along one axis. A maximum likelihood approach is applied to extract the single-particle EM from the oscillating nanoparticle position along the field-actuated axis, while mean squared displacement is used along the non-actuated axes to determine size. Unfunctionalized and carboxyl-functionalized polystyrene NPs are found to have unique EM based on their individual size and surface characteristics, and it is demonstrated that single-nanoparticle EM is a more precise tool for distinguishing unique NP preparations than diffusion alone, able to determine the charge number of individual NPs to an uncertainty of less than 30. This method also explored individual nanoparticle EM in various ionic strengths (0.25-5 mM) and found decreased EM as a function of increasing ionic strength, in agreement with results determined via bulk characterization methods. Finally, it is demonstrated that the electric field can be manipulated in real time in response to particle position, resulting in one-dimensional electrokinetic trapping. Critically, this new single-nanoparticle EM determination and trapping method does not require microfluidics, opening the possibility for the exploration of single-nanoparticle EM in close proximity to live tissue and more comprehensive characterization of nanoparticles in biologically relevant environments.

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Section: Introductionmentioning

confidence: 99%

Single-nanoparticle electrophoretic mobility determination and trapping using active-feedback 3D tracking

Johnson,

Welsher

2024

Preprint

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“…The combination of DLS and electrophoretic mobility (electrophoretic light scattering) further allows the estimation of the surface charge based on the zeta-potential distribution. Nonetheless, a relevant downside to these techniques is their bias when characterizing polydispersed systems, due to their resolution being limited to a factor of 3, potentially failing to separate multimodal particle distributions [ 7 , 8 ]. Alternative characterization techniques are mostly microscopy-based, namely, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM).…”

Section: Introductionmentioning

confidence: 99%

Characterization of Liposomes Using Quantitative Phase Microscopy (QPM)

et al. 2021

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The rapid development of nanomedicine and drug delivery systems calls for new and effective characterization techniques that can accurately characterize both the properties and the behavior of nanosystems. Standard methods such as dynamic light scattering (DLS) and fluorescent-based assays present challenges in terms of system’s instability, machine sensitivity, and loss of tracking ability, among others. In this study, we explore some of the downsides of batch-mode analyses and fluorescent labeling, while introducing quantitative phase microscopy (QPM) as a label-free complimentary characterization technique. Liposomes were used as a model nanocarrier for their therapeutic relevance and structural versatility. A successful immobilization of liposomes in a non-dried setup allowed for static imaging conditions in an off-axis phase microscope. Image reconstruction was then performed with a phase-shifting algorithm providing high spatial resolution. Our results show the potential of QPM to localize subdiffraction-limited liposomes, estimate their size, and track their integrity over time. Moreover, QPM full-field-of-view images enable the estimation of a single-particle-based size distribution, providing an alternative to the batch mode approach. QPM thus overcomes some of the drawbacks of the conventional methods, serving as a relevant complimentary technique in the characterization of nanosystems.

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Antifungal activity against Candida albicans of methyl 3,5-dinitrobenzoate loaded nanoemulsion

Duarte,

Perez-Castillo,

da Nóbrega Alves

et al. 2023

Braz J Microbiol

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Understanding Nanomedicine Size and Biological Response Dependency: What Is the Relevance of Previous Relationships Established on Only Batch-Mode DLS-Measured Sizes?

Cited by 5 publications

References 91 publications

Single-nanoparticle electrophoretic mobility determination and trapping using active-feedback 3D tracking

Single-nanoparticle electrophoretic mobility determination and trapping using active-feedback 3D tracking

Characterization of Liposomes Using Quantitative Phase Microscopy (QPM)

Antifungal activity against Candida albicans of methyl 3,5-dinitrobenzoate loaded nanoemulsion

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