Multiscale observation of biological interactions of nanocarriers: From nano to macro
Open accessAbstract
Microscopic observations have played a key role in recent advancements in nanotechnology-based biomedical sciences. In particular, multiscale observation is necessary to fully understand the nano-bio interfaces where a large amount of unprecedented phenomena have been reported. This review describes how to address the physicochemical and biological interactions of nanocarriers within the biological environments using microscopic tools. The imaging techniques are categorized based on the size scale of detection. For observation of the nanoscale biological interactions of nanocarriers, we discuss atomic force microscopy (AFM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). For the micro to macro-scale (in vitro and in vivo) observation, we focus on confocal laser scanning microscopy (CLSM) as well as in vivo imaging systems such as magnetic resonance imaging (MRI), superconducting quantum interference devices, and IVIS. Additionally, recently developed combined techniques such as AFM-CLSM, correlative light and electron microscopy (CLEM), and SEM spectroscopy are also discussed. In this review, we describe how each technique helps elucidate certain physicochemical and biological activities of nanocarriers such as dendrimers, polymers, liposomes, and polymeric/inorganic nanoparticles, thus providing a toolbox for bioengineers, pharmaceutical scientists, biologists, and research clinicians.
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AFM has also been proposed as an innovative tool for studying the mechanisms regulating nanocarrier interaction with cell membrane and their internalization.
“AFM has also been proposed as innovative tool for studying the mechanisms regulating nanocarrier interaction with cell membrane and their internalization, which are quite relevant for ensuring effective drug delivery to the target [161][162][163].”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [162]
Xiao et al. used FRET to evaluate if PEG-b-PLA micelles entered intact inside human ovarian cells or released their cargo on the plasma membrane.
“Xiao et al. [162] used FRET to evaluate if PEG-b-PLA micelles entered intact inside human ovarian cells or released their cargo on the plasma membrane.”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [162]
The Combined Systems of Multiple Imaging Technologies section mentions FRET as an imaging capability, but does not describe the claimed experiment. Searches for Xiao, PEG-b-PLA, and micelle cargo release found no passage about intact entry into human ovarian cells versus release at the plasma membrane. Page numbers were not available in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredFRET could not be observed in the case of DAF and NR alone, while an increased FRET signal in the cellular membrane was detected after treatment with both, indicating NR and DAF colocalization.
“FRET could not be observed in case of DAF and NR alone, while an increased FRET signal in the cellular membrane was detected after treatment with both, indicating NR and DAF colocalization.”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [162]
The 'Combined Systems of Multiple Imaging Technologies' section lists FRET as a capability of combined AFM and CLSM, but reports no experiment with DAF and NR. Searches for DAF, NR, and membrane FRET found no passage addressing the claimed absence of signal with either alone or the increase after treatment with both. Page numbers were not available in our copy. (LLM, conf=0.77)
Experimental — accuracy not yet measuredThis result demonstrated NR release from the micelles, since FRET cannot occur when the compound is still incorporated in the micellar core because the distance between DAF and NR is too far.
“Moreover, this result demonstrated NR release from the micelles, since FRET cannot occur when the compound is still incorporated in the micellar core because, in this case, the distance between DAF and NR is too far.”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [162]
The Combined Systems of Multiple Imaging Technologies section mentions FRET only as a capability of combined AFM and confocal microscopy. Our copy does not discuss DAF, NR release from micelles, or whether their separation in a micellar core prevents FRET (searched for those terms and the proposed mechanism). (LLM, conf=0.76)
Experimental — accuracy not yet measured
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References 110 · Cited by 42
- Authors
- Jin, S., Bae, J. W., & Hong, S.
- Affiliations
- University of Illinois Chicago (US)
- Corresponding author
- Hong, Seungpyo
- Venue
- Microscopy Research and Technique
- Publisher
- Wiley
- Published
- 2010-03-15
- Volume
- 73
- Issue
- 9
- Pages
- 813-823
- ISSN
- 1059-910X (ISSN-L)
- 1097-0029
- PMC
- PMC2930031
- OpenAlex
- W1999967093
- Cited by
- 42
- References
- 110
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 4 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 2 · 2015: 6 · 2014: 3 · 2013: 4 · 2012: 3
- FWCI
- 0.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Microscopy Research and Technique (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Center for Research Resources (C06-RR15482, C06RR015482)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Nanotechnology research and applications
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- nanocarriers, nano-bio interface, multiscale imaging, atomic force microscopy, scanning electron microscopy, transmission electron microscopy, confocal laser scanning microscopy, in vivo imaging, magnetic resonance imaging, superconducting quantum interference devices, correlative light and electron microscopy, dendrimers, liposomes, polymeric nanoparticles, inorganic nanoparticles, physicochemical interactions
- MeSH terms
- Animals, Humans, Microscopy, Particle Size, Nanomedicine, Nanoparticles
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