Noninvasive Fluorescence Resonance Energy Transfer Imaging of in Vivo Premature Drug Release from Polymeric Nanoparticles
Open accessAbstract
Understanding in vivo drug release kinetics is critical for the development of nanoparticle-based delivery systems. In this study, we developed a fluorescence resonance energy transfer (FRET) imaging approach to noninvasively monitor in vitro and in vivo cargo release from polymeric nanoparticles. The FRET donor dye (DiO or DiD) and acceptor dye (DiI or DiR) were individually encapsulated into poly(ethylene oxide)-b-polystyrene (PEO-PS) nanoparticles. When DiO (donor) nanoparticles and DiI (acceptor) nanoparticles were coincubated with cancer cells for 2 h, increased FRET signals were observed from cell membranes, suggesting rapid release of DiO and DiI to cell membranes. Similarly, increased FRET ratios were detected in nude mice after intravenous coadministration of DiD (donor) nanoparticles and DiR (acceptor) nanoparticles. In contrast, another group of nude mice i.v. administrated with DiD/DiR coloaded nanoparticles showed decreased FRET ratios. Based on the difference in FRET ratios between the two groups, in vivo DiD/DiR release half-life from PEO-PS nanoparticles was determined to be 9.2 min. In addition, it was observed that the presence of cell membranes facilitated burst release of lipophilic cargos while incorporation of oleic acid-coated iron oxide into PEO-PS nanoparticles slowed the release of DiD/DiR to cell membranes. The developed in vitro and in vivo FRET imaging techniques can be used to screening stable nanoformulations for lipophilic drug delivery.
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FRET has been utilized for observing drug release.
“In addition to MRI, optical imaging approaches, and fluorescence techniques, FRET has also been utilized for observing drug release [130,131].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [131]
The Conclusions and perspective describe using FRET imaging to measure release of lipophilic cargos from nanoparticles intended for drug delivery. The Discussion clarifies that the method measures release of fluorescent dyes and “cannot determine release kinetics of real drugs,” so this paper does not directly demonstrate observation of drug release itself. (LLM, conf=0.83)
Experimental — accuracy not yet measuredUndesired aggregation of drugs into healthy cells may cause toxicity.
“Further, undesired aggregation of drugs into healthy cells may cause toxicity [131].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [131]
The Abstract (page unavailable) says targeted delivery of anticancer drugs aims to minimize toxic side effects, and the Discussion (page unavailable) says cell membranes can trigger premature drug release before drugs reach tumors. The paper does not say that drugs aggregate in healthy cells or that such aggregation causes toxicity. (LLM, conf=0.79)
Experimental — accuracy not yet measuredHeterogeneous drug distribution happens for drugs of almost all sizes, and therapy shows no desired effect.
“Heterogeneous drug distribution happens for drugs of almost all sizes, and therapy shows no desired effect [131,132].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [131]
The Discussion (page not provided) says that some polymeric nanoparticles cannot efficiently deliver drugs to tumor sites because of premature release. It does not establish heterogeneous distribution for drugs of almost all sizes or show that therapy has no desired effect. (LLM, conf=0.84)
Experimental — accuracy not yet measured
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“Heterogeneous drug distribution happens for drugs of almost all sizes, and therapy shows no desired effect [131,132].”
BackgroundMethodImaging-assisted anticancer nanotherapy
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- Authors
- Zou, P., Chen, H., Paholak, H. J., & Sun, D.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Sun, Duxin
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2013-10-14
- Volume
- 10
- Issue
- 11
- Pages
- 4185-4194
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- PMC
- PMC3946412
- OpenAlex
- W2069009184
- Cited by
- 88
- References
- 40
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 4 · 2023: 5 · 2022: 8 · 2021: 7 · 2020: 9 · 2019: 9 · 2018: 9 · 2017: 6 · 2016: 6 · 2015: 7 · 2014: 7
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Michigan
- National Institutes of Health
- National Cancer Institute (R21CA143474, R01CA120023)
- 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 nanoparticles, drug release kinetics, burst release, lipophilic drug delivery, cancer cells
- MeSH terms
- Animals, Female, Humans, Polyethylene Glycols, Polymers, Polystyrenes, Fluorescence Resonance Energy Transfer, Cell Line, Tumor, Mice, Nanoparticles
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