Nano biomechanical engineering of agent delivery to cells

figure 1 from [1] with text explanationWhile many of us are being jabbed in the arm to deliver an agent that stimulates our immune system to recognize the coronavirus SARS-CoV-2 as a threat and destroy it, my research group has been working, in collaboration with colleagues at the European Commission Joint Research Centre, on the dynamics of nanoparticles [1] [see ‘Size matters‘ on October 23rd, 2019] which could be used as carriers for the targeted delivery of therapeutic, diagnostic and imaging agents in the human body [2].  The use of nanoparticles to mechanically stimulate stem cells to activate signalling pathways and modulate their differentiation also has some potential [3]. In studies of the efficacy of nanoparticles in these biomedical applications, the concentration of nanoparticles interacting with the cell is a primary factor influencing both the positive and negative effects.  Such studies often involve exposing a monolayer of cultured cells adhered to the bottom of container to a dose of nanoparticles and monitoring the response over a period of time.  Often, the nominal concentration of the nanoparticles in biological medium supporting the cells is reported and used as the basis for determining the dose-response relationships.  However, we have shown that this approach is inaccurate and leads to misleading results because the nanoparticles in solution are subject to sedimentation due to gravity, Brownian motion [see ‘Slow moving nanoparticles‘ on December 13th, 2017] and inter-particle forces [see ‘ Going against the flow‘ on February 3rd, 2021] which affect their transport within the medium [see graphic] and the resultant concentration adjacent to the monolayer of cells.  Our experimental results using the optical method of caustics [see ‘Holes in fluids‘ on October 22nd, 2014] have shown that nanoparticle size, colloidal stability and solution temperature influence the distribution of nanoparticles in solution.  For particles larger than 60 nm in diameter (about one thousandth of the diameter of a human hair) the nominal dose differs significantly from the dose experienced by the cells.  We have developed and tested a theoretical model that accurately describes the settling dynamics and concentration profile of nanoparticles in solution which can be used to design in vitro experiments and compute dose-response relationships.

References

[1] Giorgi F, Macko P, Curran JM, Whelan M, Worth A & Patterson EA. 2021 Settling dynamics of nanoparticles in simple and biological media. Royal Society Open Science, 8:210068.

[2] Daraee H, Eatemadi A, Abbasi E, Aval SF, Kouhi M, & Akbarzadeh A. 2016 Application of gold nanoparticles in biomedical and drug delivery. Artif. Cells Nanomed. Biotechnol. 44, 410–422. (doi:10.3109/21691401.2014.955107)

[3] Wei M, Li S, & Le W. 2017 Nanomaterials modulate stem cell differentiation: biological
interaction and underlying mechanisms. J. Nanobiotechnol. 15, 75. (doi:10.1186/s12951-
017-0310-5)

4 thoughts on “Nano biomechanical engineering of agent delivery to cells

  1. solow46

    So what you’re saying in effect is that everything looks good in theory but fails in practice. And fails to work because If you upset the natural balance there will be dire consequences to a human body.

    Reply
    1. Eann Patterson Post author

      No, that’s not what I am saying. I am saying that the dose delivered locally to the cells is not the same as the dose calculated using the number of nanoparticles and the volume of the solution containing the cells. I have said nothing about the what happens in the human body because all of our experiments were conducted on cells in a solution in a glass container.

      Reply
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