FRET Imaging Reveals Different Cellular Entry Routes of Self-Assembled and Disulfide Bonded Polymeric Micelles
Open accessAbstract
Although nanocarriers hold promise for cancer chemotherapy, their intracellular drug delivery pathways are not fully understood. In particular, the influence of nanocarrier stability on cellular uptake is still uncertain. By physically loading hydrophobic FRET probes, we revealed different intracellular drug delivery routes of self-assembled and disulfide bonded micelles. The self-assembled micelles were structurally dissociated by micelle-membrane interactions, and the hydrophobic probes were distributed on the plasma membrane. Alternatively, intact disulfide bonded micelles carrying hydrophobic probes were internalized into cancer cells via multiple endocytic pathways. Following internalization, disulfide bonded micelles were decomposed in early endosomes by glutathione-mediated disulfide bond reduction, exposing the probes to intracellular organelles.
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In specific cases, release studies can be carried out without a dialysis membrane, as with polarity-sensitive fluorescent probes and FRET.
“In specific cases, release studies could be carried out without dialysis membrane; it is the case of polarity-sensitive fluorescent probes and FRET (Foerster resonance energy transfer) use (see specific chapter) [63,91,123,124].”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [91]
The Results section (page unavailable) uses FRET imaging to observe probe release from micelles during cellular entry, and the Cellular FRET imaging methods describe an assay without a dialysis membrane. The paper does not describe release studies using polarity-sensitive fluorescent probes. Its membrane dialysis method is for micelle preparation, not the release measurement. (LLM, conf=0.86)
Experimental — accuracy not yet measuredFRET occurs only if two conditions are respected: partial overlap between the emission spectrum of the donor and the excitation spectrum of the acceptor, and the two dyes must be in close proximity (1-10 nm).
“FRET occurs only if two conditions are respected.The first one is the partial overlap between the emission spectrum of the donor and the excitation spectrum of the acceptor, to produce enough energy for dipole-dipole coupling.The second one is that the two dyes must be in close proximity (distances in the range between 1-10 nm) [91,229].”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [91]
The Results section (‘DS micelles retain payloads during cellular entry’; page unavailable) reports that adjacent DiO and DiI probes recovered FRET efficiency, supporting the close-proximity part. The Experimental section (‘Cellular FRET imaging’; page unavailable) describes excitation and detection wavelengths, but our copy does not state that donor-emission and acceptor-excitation spectra must overlap or specify a 1–10 nm distance. (LLM, conf=0.83)
Experimental — accuracy not yet measuredFRET-based strategies have been primarily proposed as effective tools for investigating micelles structural characteristics and drug loading (static characterization), in addition to structural stability, environmental responses and drug release kinetics (dynamic characterization).
“FRETbased strategies have been primary proposed as effective tools for investigating micelles structural characteristics and drug loading (the so-called static characterization), in addition to other properties including their structural stability, environmental responses and drug release kinetics (well-known as dynamic characterization) [91].”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [91]
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- Authors
- Lee, S.-Y., Tyler, J. Y., Kim, S., Park, K., & Cheng, J.-X.
- Affiliations
- Purdue University West Lafayette (US)
- Corresponding author
- Park, Kinam
- Cheng, Ji-Xin
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2013-08-15
- Volume
- 10
- Issue
- 9
- Pages
- 3497-3506
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- PMC
- PMC3946486
- OpenAlex
- W2111990201
- Cited by
- 59
- References
- 75
- Citations by year
- 2025: 4 · 2024: 5 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 8 · 2019: 2 · 2018: 10 · 2017: 3 · 2016: 7 · 2015: 8 · 2014: 4 · 2013: 1
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA129287)
- 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 › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- polymeric micelles, disulfide bond stability, FRET probes, cellular uptake, intracellular drug delivery, endocytosis, early endosomes, cancer cells, nanocarriers, self-assembly
- MeSH terms
- Cell Line, Disulfides, Glutathione, Humans, Micelles, Polymers, Fluorescence Resonance Energy Transfer, Nanomedicine, MCF-7 Cells
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