Micellar nanocontainers distribute to defined cytoplasmic organelles. Science

Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, H3G 1Y6, Canada.
Science (Impact Factor: 33.61). 05/2003; 300(5619):615-8. DOI: 10.1126/science.1078192
Source: PubMed


Block copolymer micelles are water-soluble biocompatible nanocontainers with great potential for delivering hydrophobic drugs.
An understanding of their cellular distribution is essential to achieving selective delivery of drugs at the subcellular level.
Triple-labeling confocal microscopy in live cells revealed the localization of micelles in several cytoplasmic organelles,
including mitochondria, but not in the nucleus. Moreover, micelles change the cellular distribution of and increase the amount
of the agent delivered to the cells. These micelles may thus be worth exploring for their potential to selectively deliver
drugs to specified subcellular targets.

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    • "Various processes have been proposed. For instance, fluorescent poly(ethyleneoxide-b-ε-caprolactone) (PEO-PCL) copolymer nanopaticles have been suggested to enter the cells by endocytosis (Allen et al., 1999b) and have also been reported to distribute in various intracellular organelles -lysosomes, Golgi aparatus, endoplasmic reticulum and mitochondria (Savic et al., 2003). In contrast, similar nanoparticles, made of (polyethylene glycol)-b-poly (D, L-lactide) (PEG-PDLLA), have been reported to be unable to penetrate into the cells but to transfer the entrapped drug through the plasma membrane, leading to the internalization of the drug (Chen et al., 2008). "
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    ABSTRACT: Block-polymer nanoparticles are now well-known candidates for the delivery of various non-soluble drugs to cells. The release of drugs from these nanoparticles is a major concern related to their efficiency as nanovectors and is still not completely deciphered. Various processes have been identified, depending of both the nature of the block-polymer and those of the drugs used. We focused our interest on an amphiphilic photosensitizer studied for photodynamic treatments of cancer, Pheophorbide-a (Pheo). We studied the transfer of Pheo from poly(ethyleneglycol-b-ϵ-caprolactone) nanoparticles (I) to MCF-7 cancer cells and (II) to models of membranes. Altogether, our results suggest that the delivery of the major part of the Pheo by the nanoparticles occurs via a direct transfer of Pheo from the nanoparticles to the membrane, by collision. A minor process may involve the internalization of a small amount of the nanoplatforms by the cells. So, this research illustrates the great care necessary to address the question of the choice of such nanocarriers, in relation with the properties - in particular the relative hydrophobicity - of the drugs encapsulated, and gives elements to predict the mechanism and the efficiency of the delivery.
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    • "Based on the current knowledge regarding the potential problems of Ag NPs for the environment and human health, there is a clear need to characterize them considering a number of important factors such as: size, chemical composition, shape, surface structure, surface charge, aggregation and solubility, and the presence or absence of other chemical functional groups. Many of these characteristics and thus, behavior, bioavailability, and toxicity are affected and modified by surrounding media properties, including pH, ionic concentration, presence of natural organic materials, colloids, etc. (Yu et al., 2013; Ferreira da Silva et al., 2011; Savic et al., 2003). Handling and sample preparation, as well as storage conditions, might be critical. "
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    • "Well-established in vitro methods [13] [14] have been introduced to determine delivery micelle stability; however, the passage of micelles through the bloodstream introduces much greater challenges due to shear forces, opsonization and uptake, and other undesirable interactions with off-target cells. It is, therefore, critical to monitor the integrity of micellar structures in vivo, preferably in real time. "
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    ABSTRACT: Translation of micelles from the laboratory to the clinic is limited by a poor understanding of their in vivo fate following administration. In this paper, we establish a robust approach to real-time monitoring of the in vivo stability of micelles using Förster Resonance Energy Transfer (FRET). This characterization method allows for exquisite insight into the fate of micellar constituents, affording the capabilities to rapidly and efficiently evaluate a library of synthetically derived micellar systems as new therapeutic platforms in vivo. FRET-enabled biological characterization further holds potential to tailor material systems being uniquely investigated across the delivery community towards the next generation of stable therapeutics for disease management.
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