Cited by 394Nanoparticle-Based Drug DeliveryRNA Interference and Gene DeliveryLipid Membrane Structure and Behavior

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Release of hydrophobic molecules from polymer micelles into cell membranes revealed by Förster resonance energy transfer imaging

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Chen, Hongtao, Kim, Sungwon, Li, Li, Wang, Shuyi, Park, Kinam, Cheng, Ji-Xin·2008·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0707046105PMC PMC2373326

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Abstract

It is generally assumed that polymeric micelles, upon administration into the blood stream, carry drug molecules until they are taken up into cells followed by intracellular release. The current work revisits this conventional wisdom. The study using dual-labeled micelles containing fluorescently labeled copolymers and hydrophobic fluorescent probes entrapped in the polymeric micelle core showed that cellular uptake of hydrophobic probes was much faster than that of labeled copolymers. This result implies that the hydrophobic probes in the core are released from micelles in the extracellular space. Förster resonance energy transfer (FRET) imaging and spectroscopy were used to monitor this process in real time. A FRET pair, DiIC(18(3)) and DiOC(18(3)), was loaded into monomethoxy poly(ethylene glycol)-block-poly(d,l-lactic acid) micelles. By monitoring the FRET efficiency, release of the core-loaded probes to model membranes was demonstrated. During administration of polymeric micelles to tumor cells, a decrease of FRET was observed both on the cell membrane and inside of cells, indicating the release of core-loaded probes to the cell membrane before internalization. The decrease of FRET on the plasma membrane was also observed during administration of paclitaxel-loaded micelles. Taken together, our results suggest a membrane-mediated pathway for cellular uptake of hydrophobic molecules preloaded in polymeric micelles. The plasma membrane provides a temporal residence for micelle-released hydrophobic molecules before their delivery to target intracellular destinations. A putative role of the PEG shell in the molecular transport from micelle to membrane is discussed.

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Authors: Chen, H., Kim, S., Li, L., Wang, S., Park, K., & Cheng, J.-X.
Affiliations: Purdue University West Lafayette (US)
University of Shanghai for Science and Technology (CN)
ORCID: Chen, Hongtao
Kim, Sungwon
Wang, Shuyi
Park, Kinam
Cheng, Ji-Xin
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2008-05-06
Volume: 105
Issue: 18
Pages: 6596-6601
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0707046105
PMC: PMC2373326
OpenAlex: W2033486390
Cited by: 394
References: 45
Citations by year: 2026: 8 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 17 · 2021: 18 · 2020: 28 · 2019: 27 · 2018: 31 · 2017: 30 · 2016: 28 · 2015: 31 · 2014: 37 · 2013: 32 · 2012: 36
FWCI: 7.90
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Purdue e-Pubs (Purdue University System) (submittedVersion)
Funders: National Science Foundation (0416785)
Purdue University
National Institutes of Health
National Heart, Lung, and Blood Institute (R01HL078715, R56HL078715, HL078715)
National Institute of General Medical Sciences (R01GM065284, GM065284)
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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords: polymeric micelles, hydrophobic drug release, cellular uptake, plasma membrane, paclitaxel, cancer cells
MeSH terms: Caproates, Cell Membrane, Endocytosis, HeLa Cells, Humans, Lactones, Micelles, Microscopy, Fluorescence, Polyethylene Glycols, Polymers, Molecular Probes, Paclitaxel, Lactic Acid, Fluorescence Resonance Energy Transfer, Hydrophobic and Hydrophilic Interactions

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Release of hydrophobic molecules from polymer micelles into cell membranes revealed by Förster resonance energy transfer imaging

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