Ultrabright Fluorescent Polymeric Nanoparticles with a Stealth Pluronic Shell for Live Tracking in the Mouse Brain
Open accessAbstract
Visualizing single organic nanoparticles (NPs) in vivo remains a challenge, which could greatly improve our understanding of the bottlenecks in the field of nanomedicine. To achieve high single-particle fluorescence brightness, we loaded polymer poly(methyl methacrylate)-sulfonate (PMMA-SO 3 H) NPs with octadecyl rhodamine B together with a bulky hydrophobic counterion (perfluorinated tetraphenylborate) as a fluorophore insulator to prevent aggregation-caused quenching. To create NPs with stealth properties, we used the amphiphilic block copolymers pluronic F-127 and F-68. Fluorescence correlation spectroscopy and Förster resonance energy transfer (FRET) revealed that pluronics remained at the NP surface after dialysis (at one amphiphile per 5.5 nm 2 ) and prevented NPs from nonspecific interactions with serum proteins and surfactants. In primary cultured neurons, pluronics stabilized the NPs, preventing their prompt aggregation and binding to neurons. By increasing dye loading to 20 wt % and optimizing particle size, we obtained 74 nm NPs showing 150-fold higher single-particle brightness with two-photon excitation than commercial Nile Red-loaded FluoSpheres of 39 nm hydrodynamic diameter. The obtained ultrabright pluronic-coated NPs enabled direct single-particle tracking in vessels of mice brains by two-photon intravital microscopy for at least 1 h, whereas noncoated NPs were rapidly eliminated from the circulation. Following brain injury or neuroinflammation, which can open the blood–brain barrier, extravasation of NPs was successfully monitored. Moreover, we demonstrated tracking of individual NPs from meningeal vessels until their uptake by meningeal macrophages. Thus, single NPs can be tracked in animals in real time in vivo in different brain compartments and their dynamics visualized with subcellular resolution.
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The bright fluorescence emitted by these particles allowed separation of individual particles, tracking their trajectories in blood vessels, and acquiring images with a high signal-to-noise ratio up to 800 μm depth.
“The bright fluorescence emitted by these particles allowed for the separation of individual particles, allowing one to track their trajectories in the blood vessels and acquire images with a high signal-to-noise ratio up to 800 μm depth.”
From The Pursuit of Shortwave Infrared-Emitting Nanoparticles with Bright Fluorescence through Molecular Design and Excited-State Engineering of Molecular Aggregates (2022) · cites this paper as [214]
These nanoparticles were further applied in live imaging of mouse brain by two-photon excitation at 780 nm.
“These nanoparticles were further applied in live imaging of mouse brain by two-photon excitation at 780 nm.”
From The Pursuit of Shortwave Infrared-Emitting Nanoparticles with Bright Fluorescence through Molecular Design and Excited-State Engineering of Molecular Aggregates (2022) · cites this paper as [214]
Visualization of NIR emitting single organic nanoparticles in vivo was demonstrated using octadecyl rhodamine B dye loaded with the assist of bulky hydrophobic counterion (perfluorinated tetraphenylborate) in poly(methyl methacrylate)-sulfonate nanoparticles as a fluorophore insulator.
“A visualization of NIR emitting single organic nanoparticles in vivo was demonstrated using octadecyl rhodamine B dye loaded with the assist of bulky hydrophobic counterion (perfluorinated tetraphenylborate) in poly(methyl methacrylate)-sulfonate nanoparticles (PMMA-SO3H) as a fluorophore insulator.214”
From The Pursuit of Shortwave Infrared-Emitting Nanoparticles with Bright Fluorescence through Molecular Design and Excited-State Engineering of Molecular Aggregates (2022) · cites this paper as [214]
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Complexation of HSA with the Medicine Quercetin
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Self-citationNeutrophil‐Mimetic MRI Enables Ultra‐Early Detection of Vascular Inflammation After Stroke
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Self-citation
- Authors
- Khalin, I., Heimburger, D., Melnychuk, N., Collot, M., Groschup, B., Hellal, F., Reisch, A., Plesnila, N., & Klymchenko, A. S.
- Affiliations
- Institut für Schlaganfall- und Demenzforschung (DE)
- Centre National de la Recherche Scientifique (FR)
- Munich Cluster for Systems Neurology (DE)
- Corresponding author
- Reisch, Andreas
- Plesnila, Nikolaus
- Klymchenko, Andrey S.
- ORCID
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-07-17
- Volume
- 14
- Issue
- 8
- Pages
- 9755-9770
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- OpenAlex
- W3043568696
- Cited by
- 82
- References
- 91
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 18 · 2023: 11 · 2022: 17 · 2021: 16 · 2020: 4
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- green
- hal.science
- Licence
- Locations
- ACS Nano (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-16-CE09-0007)
- H2020 Marie Sklodowska-Curie Actions (794094)
- Horizon 2020 Framework Programme (680966)
- Alexander von Humboldt-Stiftung
- H2020 European Research Council (648528)
- Synergy Munich Cluster
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
- Physical Sciences › Materials Science › Materials Chemistry › Quantum Dots Synthesis And Properties
- Keywords
- single-particle tracking, fluorescent nanoparticles, aggregation-caused quenching, Pluronic block copolymers, stealth coatings, blood-brain barrier, meningeal macrophages, neuroinflammation, brain injury, nanoparticle extravasation, nanoparticle aggregation
- MeSH terms
- Animals, Brain, Fluorescent Dyes, Particle Size, Polymers, Poloxamer, Mice, Nanoparticles
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