Effect of Ligand Shell Composition on Biodistribution of Ultrasmall Gold Nanoparticles

Cytotoxic chemotherapy is the standard of care for many types of cancer despite the frequently observed severe side effects. The targeted delivery of chemotherapeutics has great potential to reduce these effects by increasing... [ view full abstract ]

Cytotoxic chemotherapy is the standard of care for many types of cancer despite the frequently observed severe side effects. The targeted delivery of chemotherapeutics has great potential to reduce these effects by increasing drug concentrations within the target tissue, thereby reducing the required dose [1]. Targeted delivery can be an extremely useful approach to achieving a therapeutically active concentration whilst ensuring acceptable systemic toxicity [2].

Midatech Pharma Plc uses novel ultrasmall gold nanoparticles (GNPs) with a gold core diameter of 1.6 – 1.8 nm as a functionalizable vehicle for tissue-selective delivery (Figure 1). This platform is highly flexible, allowing incorporation of various components dependent upon the therapeutic application [3]. In the current study we describe GNPs that are coated with thiol-modified carbohydrates and bifunctional polyethylene glycols (PEGs).

We investigated the effect of different chemical ligand shell compositions on the biodistribution and pharmacokinetic profile of these particles using an in vivo rat model. By varying the charge and ligand size, we showed that Midatech’s novel ultrasmall gold nanoparticles can be customized to vary circulation times and tissue selective accumulation. Also, due to their very small size and carbohydrate based ligand shell these particles are less likely to form a protein corona compared to larger nanoparticle analogues [4], and are therefore especially interesting candidates for active targeting strategies.

In conclusion, Midatech GNPs offer a highly flexible and customizable drug delivery system which may be tailored for a range of cancer types and other diseases.


References

[1] S. M. Sagnella, J. A. McCarroll, M. Kavallaris, Nanomedicine, 10, 1131 (2014).
[2] M. Shilo, M. Motiei, P. Hana, R. Popovtzer, Nanoscale, 6, 2146 (2014).
[3] midatechpharma.com.
[4] K. Zarschler, L. Rocks, N. Licciardello, L. Boselli, E. Polo, K. P. Garcia, L. De Cola, H. Stephan, K. A. Dawson, Nanomedicine, 12 (6), 1663-1701.