ArticleProceedings of the National Academy of Sciences of the United States of America2008
Release of hydrophobic molecules from polymer micelles into cell membranes revealed by Forster resonance energy transfer imaging.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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Who cites it
118 citing papers in PubMed, 383 citations in OpenAlex.
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- Micelle-in-Liposomes for Sustained Delivery of Anticancer Agents That Promote Potent TRAIL-Induced Cancer Cell Apoptosis.Molecules (Basel, Switzerland) · 2020Article
- A combined "eat me/don't eat me" strategy based on extracellular vesicles for anticancer nanomedicine.Journal of extracellular vesicles · 2020Article
- Polymers prepared through an "ATRP polymerization-esterification" strategy for dual temperature- and reduction-induced paclitaxel delivery.RSC advances · 2020Article
- Toward understanding polymer micelle stability: Density ultracentrifugation offers insight into polymer micelle stability in human fluids.Journal of controlled release : official journal of the Controlled Release Society · 2020Article
58 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.