In Vivo Characterization of Dynein-Driven nanovectors Using Drosophila Oocytes

Parassol, Nadège; Bienvenu, Céline; Boglio, Cécile; Fiorucci, Sébastien; Cerezo, Delphine; Yu, Xiaomin; Godeau, Guilhem; Greiner, Jacques; Vierling, Pierre; Noselli, Stéphane; Giorgio, Christophe Di; Bor, Véronique Van De

doi:10.1371/journal.pone.0082908

Cited by 3 publications

(1 citation statement)

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“…, Au@DBPs), which may be highly useful in the drug delivery area. These results are in agreement with previous reports that employed soft carriers, such as microspheres [ 41 ] or liposomes [ 42 ], functionalized with dynein light chain 8 (LC8) peptide binding motifs. Similarly, in the present work, we selected peptides able to bind a dynein chain with very high affinity [ 31 ], which were linked to hard Au@tiopronin NPs.…”

Section: Discussionsupporting

confidence: 93%

Nanoparticles engineered to bind cellular motors for efficient delivery

et al. 2018

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BackgroundDynein is a cytoskeletal molecular motor protein that transports cellular cargoes along microtubules. Biomimetic synthetic peptides designed to bind dynein have been shown to acquire dynamic properties such as cell accumulation and active intra- and inter-cellular motion through cell-to-cell contacts and projections to distant cells. On the basis of these properties dynein-binding peptides could be used to functionalize nanoparticles for drug delivery applications.ResultsHere, we show that gold nanoparticles modified with dynein-binding delivery sequences become mobile, powered by molecular motor proteins. Modified nanoparticles showed dynamic properties, such as travelling the cytosol, crossing intracellular barriers and shuttling the nuclear membrane. Furthermore, nanoparticles were transported from one cell to another through cell-to-cell contacts and quickly spread to distant cells through cell projections.ConclusionsThe capacity of these motor-bound nanoparticles to spread to many cells and increasing cellular retention, thus avoiding losses and allowing lower dosage, could make them candidate carriers for drug delivery.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0354-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 93%

Nanoparticles engineered to bind cellular motors for efficient delivery

et al. 2018

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Intracellular trafficking of a dynein-based nanoparticle designed for gene delivery

Favaro¹,

Unzueta

Cabo

et al. 2018

European Journal of Pharmaceutical Sciences

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The success of viruses in the delivery of the viral genome to target cells relies on the evolutionary selection of protein-based domains able to hijack the intermolecular interactions through which cells respond to intra- and extracellular stimuli. In an effort to mimic viral infection capabilities during non-viral gene delivery, a modular recombinant protein named T-Rp3 was recently developed, containing a DNA binding domain, a dynein molecular motor interacting domain, and a TAT-derived transduction domain. Here, we analyzed at the microscopic level the mechanisms behind the cell internalization and intracellular trafficking of this highly efficient modular protein vector. We found that the protein has the ability to self-assemble in discrete protein nanoparticles resembling viral capsids, to bind and condense plasmid DNA (pDNA), and to interact with eukaryotic cell membranes. Confocal and single particle tracking assays performed on living HeLa cells revealed that the T-Rp3 nanoparticles promoted an impressive speed of cellular uptake and perinuclear accumulation. Finally, the protein demonstrated to be a versatile vector, delivering siRNA at efficiencies comparable to Lipofectamine™. These results demonstrate the high potential of recombinant modular proteins with merging biological functions to fulfill several requirements needed to obtain cost-effective non-viral vectors for gene-based therapies.

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