Biological Obstacles of Gold Nanoparticles

Gold nanoparticles are between 1–100 nm in diameter and show great potential as drug delivery vehicles, contrast agents, biosensors, and radiation dose enhancers. However, basic understanding of how the physical and chemical properties of these particles interact with a biological environment is lacking.

Upon intravenous administration, nanoparticles must overcome opsonisation and clearance by reticuloendothelial system, locate tumors, penetrate target cells to deliver drugs, and be safely eliminated from the body without bioaccumulation. The ability to bypass these obstacles is dependent on the physical dimensions and chemical properties of the nanoparticle.

Gold nanoparticles of various shapes obtained by laser ablation in water. Image Credit: Georgy Shafeev / Shutterstock
Gold nanoparticles of various shapes obtained by laser ablation in water. Image Credit: Georgy Shafeev / Shutterstock

Nanoparticle Surface Chemistry

Proteins present in the blood accumulate on foreign bodies, such as nanoparticles for uptake and excretion by phagocytotic cells. The formation of these proteins around the nanoparticle is known as a protein corona prevents the drug delivery functions of nanoparticles.

Poly-ethylene glycol (PEG) is commonly used to coat nanoparticles for in vivo use, as it is biocompatible and prevents the formation of the protein corona. Overexpressed membrane proteins on cancer cells can be exploited by targeting complimentary biomolecules which can be internalised along with the nanoparticle by active transport mechanisms.

Very large nanoparticles, or those that have become several times larger than they were initially due to the formation of the protein corona, have difficulty passing through the renal filtration system of the liver.

Alternatively, these particles may be excreted by the hepatobiliary system, which takes significantly longer. Zwitterionic coatings encourage renal clearance more effectively than positively or negatively charged coatings, while also offering better resistance to protein accumulation.

Gold Nanoparticle - Sixty Symbols

Nanoparticle Geometry

Large gold nanoparticles

Larger gold nanoparticles possess a larger surface area and greater affinity for proteins than smaller nanoparticles. This is due to the increasing curvature of the nanoparticle surface with reduced diameter, providing a less flat surface to bind through van der Waals forces. Thus, nanoparticles of shapes other than sphere demonstrate different affinities of protein corona formation. Nanorods demonstrate ten times the protein accumulation compared to spheres due to a much greater flat surface area.

Intermediate size gold nanoparticles

Gold nanoparticles of around 50 nm in diameter show the most uptake by cells compared to larger or smaller nanoparticles. Nanoparticles require the cell membrane to wrap around them prior to internalization, costing energy. Larger particles cost more energy to wrap with the cell membrane due to their size, while smaller particles also cost more energy as they require greater curvature to enwrap them. However, surface chemistry plays a greater role in the rate of internalization. Similarly, particles of shapes possessing a large surface-to-volume ratio are less favoured than spheres for cell internalization, as the cell membrane must wrap around a far greater area with increasing aspect ratio.

Smaller nanoparticles

Smaller nanoparticles penetrate tumor tissue more effectively than large ones, as tumors are packed with cells and extracellular matrices that make navigation difficult. Shape also effects the diffusion of nanoparticles where rod and cuboidal cage gold nanoparticles penetrate more deeply compared with spherical particles due to the smaller diameter of rods and the lower density of hollow cuboidal cage particles. This makes them less susceptible to increased interstitial fluid.

Excretion of nanoparticles

Excretion is also affected by the size and shape of the nanoparticle, as it must pass through a pore size of a particular diameter. Thus, particles with a dimension lower than this pore size, such as rods or small spheres, are more effectively excreted.


Further Reading

Last Updated: Oct 15, 2018

Michael Greenwood

Written by

Michael Greenwood

Michael graduated from the University of Salford with a Ph.D. in Biochemistry in 2023, and has keen research interests towards nanotechnology and its application to biological systems. Michael has written on a wide range of science communication and news topics within the life sciences and related fields since 2019, and engages extensively with current developments in journal publications.  


Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Greenwood, Michael. (2018, October 15). Biological Obstacles of Gold Nanoparticles. News-Medical. Retrieved on February 28, 2024 from

  • MLA

    Greenwood, Michael. "Biological Obstacles of Gold Nanoparticles". News-Medical. 28 February 2024. <>.

  • Chicago

    Greenwood, Michael. "Biological Obstacles of Gold Nanoparticles". News-Medical. (accessed February 28, 2024).

  • Harvard

    Greenwood, Michael. 2018. Biological Obstacles of Gold Nanoparticles. News-Medical, viewed 28 February 2024,


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
You might also like...
Breakthrough nano-shield blocks selective allergic reactions