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Simultaneous, Single-Particle Measurements of Size and Loading Give Insights into the Structure of Drug-Delivery Nanoparticles.
Kamanzi, Albert; Gu, Yifei; Tahvildari, Radin; Friedenberger, Zachary; Zhu, Xingqi; Berti, Romain; Kurylowicz, Marty; Witzigmann, Dominik; Kulkarni, Jayesh A; Leung, Jerry; Andersson, John; Dahlin, Andreas; Höök, Fredrik; Sutton, Mark; Cullis, Pieter R; Leslie, Sabrina.
Afiliación
  • Kamanzi A; Department of Physics, McGill University, 3600 University, Montreal Quebec, Canada H3A2T8.
  • Gu Y; Department of Physics Astronomy, University of British Columbia, 6224 Agricultural Road, Vancouver, British Columbia, Canada V6T 1Z1.
  • Tahvildari R; Michael Smith Laboratories and Department of Physics, University of British Columbia, 2329 West Mall, Vancouver, British Columbia, Canada V6T 1Z4.
  • Friedenberger Z; Department of Physics, McGill University, 3600 University, Montreal Quebec, Canada H3A2T8.
  • Zhu X; Department of Physics, McGill University, 3600 University, Montreal Quebec, Canada H3A2T8.
  • Berti R; Department of Physics, McGill University, 3600 University, Montreal Quebec, Canada H3A2T8.
  • Kurylowicz M; Department of Physics, McGill University, 3600 University, Montreal Quebec, Canada H3A2T8.
  • Witzigmann D; Department of Physics, McGill University, 3600 University, Montreal Quebec, Canada H3A2T8.
  • Kulkarni JA; Michael Smith Laboratories and Department of Physics, University of British Columbia, 2329 West Mall, Vancouver, British Columbia, Canada V6T 1Z4.
  • Leung J; ScopeSys Inc., 33 Rue Prince, Montreal, Quebec, Canada H3C 2M7.
  • Andersson J; Department of Physics, McGill University, 3600 University, Montreal Quebec, Canada H3A2T8.
  • Dahlin A; ScopeSys Inc., 33 Rue Prince, Montreal, Quebec, Canada H3C 2M7.
  • Höök F; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
  • Sutton M; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
  • Cullis PR; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
  • Leslie S; Department of Chemistry and Chemical Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden.
ACS Nano ; 15(12): 19244-19255, 2021 12 28.
Article en En | MEDLINE | ID: mdl-34843205
Nanoparticles are a promising solution for delivery of a wide range of medicines and vaccines. Optimizing their design depends on being able to resolve, understand, and predict biophysical and therapeutic properties, as a function of design parameters. While existing tools have made great progress, gaps in understanding remain because of the inability to make detailed measurements of multiple correlated properties. Typically, an average measurement is made across a heterogeneous population, obscuring potentially important information. In this work, we develop and apply a method for characterizing nanoparticles with single-particle resolution. We use convex lens-induced confinement (CLiC) microscopy to isolate and quantify the diffusive trajectories and fluorescent intensities of individual nanoparticles trapped in microwells for long times. First, we benchmark detailed measurements of fluorescent polystyrene nanoparticles against prior data to validate our approach. Second, we apply our method to investigate the size and loading properties of lipid nanoparticle (LNP) vehicles containing silencing RNA (siRNA), as a function of lipid formulation, solution pH, and drug-loading. By taking a comprehensive look at the correlation between the intensity and size measurements, we gain insights into LNP structure and how the siRNA is distributed in the LNP. Beyond introducing an analytic for size and loading, this work allows for future studies of dynamics with single-particle resolution, such as LNP fusion and drug-release kinetics. The prime contribution of this work is to better understand the connections between microscopic and macroscopic properties of drug-delivery vehicles, enabling and accelerating their discovery and development.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Portadores de Fármacos / Nanopartículas Idioma: En Revista: ACS Nano Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Portadores de Fármacos / Nanopartículas Idioma: En Revista: ACS Nano Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos