Gold-labeled block copolymer micelles reveal gold aggregates at multiple subcellular sites
Abstract
There is increasing interest in the usefulness of block copolymer micelles as drug delivery vehicles. However, their subcellular distribution has not been explored extensively, mostly because of the lack of adequately labeled block copolymers. In a previous study, we showed that fluorescently labeled block copolymer micelles entered living cells and co-localized with cytoplasmic organelles selectively labeled with fluorescent dyes. The details of the observed co-localizations were, however, limited by the resolution of the fluorescence approach, which is ca. 500 nm. Using transmission electron microscopy (TEM), we established time- and concentration-dependent subcellular distributions of gold-labeled micelles within human embryonic kidney (HEK 293) cells and human lung carcinoma (A549) cells. Gold particles were incorporated into poly(4-vinylpyridine)-block-poly(ethylene oxide) (P4VP21-b-PEO45) micelles. Data from dynamic light scattering (DLS) and TEM analyses revealed that the sizes of the gold particles ranged from 4 to 8 nm. The cells survived up to 24 h in the presence of low gold-labeled micelle concentrations (0.73 microg/mL), but cell death occurred at higher concentrations (i.e., kidney cells are more susceptible than lung cells). Over 24 h periods of equivalent exposure, lung cells internalized significantly more gold-incorporated micelles than kidney cells. Although micelles were added to the cell culture media as dispersed colloidal particles, the presence of serum in these media caused aggregation. These aggregates occurred mainly close to the cell plasma membrane at early times (5-10 min); however, at later times (24 h) aggregated particles were seen inside endosomes and lysozomes. Thus, gold-incorporated (labeled) micelles can serve as a valuable extension of the fluorescence approach to visualizing the localization of micelles in subcellular compartments, improving the resolution by at least 20-fold.
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TEM results often, though not always, demonstrated agreement with cryo-TEM observations.
“whose results often (even if not always [170]) demonstrated to be in agreement with cryo-TEM observations [169,171].”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [171]
The majority of micelles morphological evaluations found in the literature are performed using TEM.
“the majority of micelles morphological evaluations found in the literature are performed by using TEM”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [171]
cryo-TEM is recognized as a more suitable tool for micelles imaging than standard TEM.
“despite cryo-TEM is recognized as a more suitable tool for micelles imaging than standard TEM”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [171]
The same morphological differences between the two populations of PLA-b-PAA micelles were found by cryo-TEM, providing confidence for TEM use.
“The same morphological differences between the two populations of micelles were found also by observation with cryo-TEM, providing confidence for TEM use.”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [171]
For PLA-b-PAA micelles, standard TEM showed cylindrical micelles for enantiomers and spherical nanostructures for the racemic mixture.
“By using standard TEM, micelles appeared cylindrical for enantiomers, whereas in case of the racemic mixture spherical nanostructures were visualized.”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [171]
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- Authors
- Lim Soo, P., Sidorov, S. N., Mui, J., Bronstein, L. M., Vali, H., Eisenberg, A., & Maysinger, D.
- Affiliations
- Department of Chemistry, McGill University, 801 Sherbrooke Street W., Montreal, Quebec, Canada H3A 2K6, Nesmeyanov Institute of Organoelement Compounds RAS, 28 Vavilov Str., Moscow, Russia 119991, Facility for Electron Microscopy Research, McGill University, 3640 University Street, Montreal, Quebec, Canada H3A 2B2, Department of Chemistry, Indiana University, 800 E. Kirkwood Avenue, Bloomington, Indiana 47405-7012, Department of Anatomy and Cell Biology, McGill University, 3640 University Street,...
- A. N. Nesmeyanov Institute of Organoelement Compounds (RU)
- Corresponding author
- Eisenberg, Adi
- Venue
- Langmuir
- Publisher
- American Chemical Society (ACS)
- Published
- 2007-03-29
- Volume
- 23
- Issue
- 9
- Pages
- 4830-4836
- ISSN
- 0743-7463 (ISSN-L)
- 1520-5827
- OpenAlex
- W2026271195
- Cited by
- 21
- References
- 43
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 3 · 2021: 1 · 2018: 1 · 2016: 1 · 2013: 1
- FWCI
- 1.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Langmuir (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Electronic, Optical and Magnetic Materials › Gold and Silver Nanoparticles Synthesis and Applications
- Keywords
- block copolymer micelles, gold nanoparticles, subcellular localization, cellular internalization, micelle aggregation, drug carriers, endosomes, lysosomes, HEK293 cells, A549 cells, cytotoxicity, transmission electron microscopy imaging
- MeSH terms
- Cell Survival, Dose-Response Relationship, Drug, Gold, Humans, Lysosomes, Micelles, Particle Size, Polyethylene Glycols, Polymers, Endosomes, Staining and Labeling, Structure-Activity Relationship, Surface Properties, Vinyl Compounds, Cell Line, Tumor
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