Investigation of the in vivo integrity of polymeric micelles via large Stokes shift fluorophore-based FRET
Abstract
Polymeric micelles hold great potential for anticancer drug delivery. Sufficient integrity of polymeric micelles after intravenous injection is critical for successful drug delivery to solid tumors, but accurate measurement of the in vivo micellar integrity remains challenging. Methods based on Förster resonance energy transfer (FRET) to monitor the in vivo micellar integrity are frequently used. However, the self-quenching effect of these FRET fluorophores used has been improperly ignored and has caused inaccurate measurements. Herein, we report a FRET-based approach using the large Stokes shift (LSS) fluorophores NBD-X and MS735 as the donor and acceptor, respectively, to investigate the integrity of polyethylene glycol-block-poly(ε-caprolactone) (PEG-PCL) micelles. We established a mathematical formula for the integrity calculation, and an in vitro verification experiment showed that the formula results exactly matched the simulated results. Our results demonstrated that PEG-PCL micelles gradually dissociated in blood circulation, but approximately 60% of the micelles in plasma remained intact 72 h after intravenous (i.v.) injection. This LSS fluorophore-based FRET approach can be used to accurately monitor the integrity of nanoparticles, and this study demonstrates that most of PEG-PCL micelles maintain their aggregation state during blood circulation for anticancer drug delivery.
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FRET imaging in mice bearing subcutaneous HepG2 tumor showed that in blood vessels 80% of injected PEG-PCL or PEG-PDLLA micelles quickly dissociate into unimers, while the remaining 20% penetrate intact into the tumoral tissue.
“FRET-imaging (covalently bound dyes: Cy5 and Cy5.5) in a mice model bearing subcutaneous HepG2 tumor highlighted that in blood vessels the 80% of injected micelles made either of polyethylene glycol-block-poly(ε-caprolactone) (PEG-PCL) or PEG-block-poly(d,l-lactide) (PEG-PDLLA) quickly dissociate into unimers, while the remaining micelles (20%), penetrate, intact, the tumoral tissue.”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [236]
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- Authors
- Zhang, H., Li, H., Cao, Z., Du, J., Yan, L., & Wang, J.
- Affiliations
- University of Science and Technology of China (CN)
- South China University of Technology (CN)
- Key Laboratory of Guangdong Province (CN)
- Guangzhou Regenerative Medicine and Health Guangdong Laboratory (CN)
- Corresponding author
- Yan, Lifeng
- Wang, Jun
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 324
- Pages
- 47-54
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W3021247595
- Cited by
- 45
- References
- 40
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 12 · 2023: 7 · 2022: 9 · 2021: 4 · 2020: 4
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Key R&D Program of China (2017YFA0205600)
- National Natural Science Foundation of China (51903089, 31771091, 51633008, 51903088, 51922043)
- Young Elite Scientists Sponsorship Program (2018QNRC001)
- Program for Guangdong Introducing Innovative and Entrepreneurial Teams (2017ZT07S054)
- Natural Science Foundation of Guangdong Province (2018A030313993, 2018A030310369)
- Guangdong Provincial Pearl River Talents Program (2017GC010713, 2017GC010304)
- Outstanding Scholar Program of Guangzhou Regenerative Medicine
- Health Guangdong Laboratory (2018GZR110102001)
- Open Project of Key Laboratory of Biomedical Engineering of Guangdong Province (KLBEMGD202003)
- Fundamental Research Funds for the Central Universities (2018MS88)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- polymeric micelles, in vivo monitoring, fluorescence resonance energy transfer, PEG-PCL, self-quenching, anticancer drug delivery, nanoparticle aggregation
- MeSH terms
- Humans, Micelles, Neoplasms, Polyesters, Polyethylene Glycols, Polymers, Drug Delivery Systems, Fluorescence Resonance Energy Transfer
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