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Light-triggered mechanical disruption of extracellular barriers by swarms of enzyme-powered nanomotors for enhanced delivery

(2023) ACS NANO. 17(8). p.7180-7193
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Abstract
Targeted drug delivery depends on the ability of nanocarriers to reach the target site, which requires the penetration of different biological barriers. Penetration is usually low and slow because of passive diffusion and steric hindrance. Nanomotors (NMs) have been suggested as the next generation of nanocarriers in drug delivery due to their autonomous motion and associated mixing hydrodynamics, especially when acting collectively as a swarm. Here, we explore the concept of enzyme-powered NMs designed as such that they can exert disruptive mechanical forces upon laser irradiation. The urease-powered motion and swarm behavior improve translational movement compared to passive diffusion of state-of-the-art nano carriers, while optically triggered vapor nanobubbles can destroy biological barriers and reduce steric hindrance. We show that these motors, named Swarm 1, collectively displace through a microchannel blocked with type 1 collagen protein fibers (barrier model), accumulate onto the fibers, and disrupt them completely upon laser irradiation. We evaluate the disruption of the microenvironment induced by these NMs (Swarm 1) by quantifying the efficiency by which a second type of fluorescent NMs (Swarm 2) can move through the cleared microchannel and be taken up by HeLa cells at the other side of the channel. Experiments showed that the delivery efficiency of Swarm 2 NMs in a clean path was increased 12-fold in the presence of urea as fuel compared to when no fuel was added. When the path was blocked with the collagen fibers, delivery efficiency dropped considerably and only depicted a 10-fold enhancement after pretreatment of the collagen-filled channel with Swarm 1 NMs and laser irradiation. The synergistic effect of active motion (chemically propelled) and mechanical disruption (light-triggered nanobubbles) of a biological barrier represents a clear advantage for the improvement of therapies which currently fail due to inadequate passage of drug delivery carriers through biological barriers.
Keywords
General Physics and Astronomy, General Engineering, General Materials Science, nanomotors, swarming, enzyme catalysis, drug delivery, vapor nanobubbles, nanoparticles

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MLA
Fraire, Juan, et al. “Light-Triggered Mechanical Disruption of Extracellular Barriers by Swarms of Enzyme-Powered Nanomotors for Enhanced Delivery.” ACS NANO, vol. 17, no. 8, 2023, pp. 7180–93, doi:10.1021/acsnano.2c09380.
APA
Fraire, J., Guix, M., Hortelao, A. C., Ruiz-González, N., Bakenecker, A. C., Ramezani, P., … Sánchez, S. (2023). Light-triggered mechanical disruption of extracellular barriers by swarms of enzyme-powered nanomotors for enhanced delivery. ACS NANO, 17(8), 7180–7193. https://doi.org/10.1021/acsnano.2c09380
Chicago author-date
Fraire, Juan, Maria Guix, Ana C. Hortelao, Noelia Ruiz-González, Anna C. Bakenecker, Pouria Ramezani, Charlotte Hinnekens, et al. 2023. “Light-Triggered Mechanical Disruption of Extracellular Barriers by Swarms of Enzyme-Powered Nanomotors for Enhanced Delivery.” ACS NANO 17 (8): 7180–93. https://doi.org/10.1021/acsnano.2c09380.
Chicago author-date (all authors)
Fraire, Juan, Maria Guix, Ana C. Hortelao, Noelia Ruiz-González, Anna C. Bakenecker, Pouria Ramezani, Charlotte Hinnekens, Félix Sauvage, Stefaan De Smedt, Kevin Braeckmans, and Samuel Sánchez. 2023. “Light-Triggered Mechanical Disruption of Extracellular Barriers by Swarms of Enzyme-Powered Nanomotors for Enhanced Delivery.” ACS NANO 17 (8): 7180–7193. doi:10.1021/acsnano.2c09380.
Vancouver
1.
Fraire J, Guix M, Hortelao AC, Ruiz-González N, Bakenecker AC, Ramezani P, et al. Light-triggered mechanical disruption of extracellular barriers by swarms of enzyme-powered nanomotors for enhanced delivery. ACS NANO. 2023;17(8):7180–93.
IEEE
[1]
J. Fraire et al., “Light-triggered mechanical disruption of extracellular barriers by swarms of enzyme-powered nanomotors for enhanced delivery,” ACS NANO, vol. 17, no. 8, pp. 7180–7193, 2023.
@article{01HGJ8ZP11GT8ENVRNP1200W3Y,
  abstract     = {{Targeted drug delivery depends on the ability of nanocarriers to reach the target site, which requires the penetration of different biological barriers. Penetration is usually low and slow because of passive diffusion and steric hindrance. Nanomotors (NMs) have been suggested as the next generation of nanocarriers in drug delivery due to their autonomous motion and associated mixing hydrodynamics, especially when acting collectively as a swarm. Here, we explore the concept of enzyme-powered NMs designed as such that they can exert disruptive mechanical forces upon laser irradiation. The urease-powered motion and swarm behavior improve translational movement compared to passive diffusion of state-of-the-art nano carriers, while optically triggered vapor nanobubbles can destroy biological barriers and reduce steric hindrance. We show that these motors, named Swarm 1, collectively displace through a microchannel blocked with type 1 collagen protein fibers (barrier model), accumulate onto the fibers, and disrupt them completely upon laser irradiation. We evaluate the disruption of the microenvironment induced by these NMs (Swarm 1) by quantifying the efficiency by which a second type of fluorescent NMs (Swarm 2) can move through the cleared microchannel and be taken up by HeLa cells at the other side of the channel. Experiments showed that the delivery efficiency of Swarm 2 NMs in a clean path was increased 12-fold in the presence of urea as fuel compared to when no fuel was added. When the path was blocked with the collagen fibers, delivery efficiency dropped considerably and only depicted a 10-fold enhancement after pretreatment of the collagen-filled channel with Swarm 1 NMs and laser irradiation. The synergistic effect of active motion (chemically propelled) and mechanical disruption (light-triggered nanobubbles) of a biological barrier represents a clear advantage for the improvement of therapies which currently fail due to inadequate passage of drug delivery carriers through biological barriers.}},
  author       = {{Fraire, Juan and Guix, Maria and Hortelao, Ana C. and Ruiz-González, Noelia and Bakenecker, Anna C. and Ramezani, Pouria and Hinnekens, Charlotte and Sauvage, Félix and De Smedt, Stefaan and Braeckmans, Kevin and Sánchez, Samuel}},
  issn         = {{1936-0851}},
  journal      = {{ACS NANO}},
  keywords     = {{General Physics and Astronomy,General Engineering,General Materials Science,nanomotors,swarming,enzyme catalysis,drug delivery,vapor nanobubbles,nanoparticles}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{7180--7193}},
  title        = {{Light-triggered mechanical disruption of extracellular barriers by swarms of enzyme-powered nanomotors for enhanced delivery}},
  url          = {{http://doi.org/10.1021/acsnano.2c09380}},
  volume       = {{17}},
  year         = {{2023}},
}

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