2.3 Gold nanoparticles in biological applications
2.3.3 Drug and gene delivery vehicles
Gold nanoparticles can be utilized for the delivery of therapeutic molecules into the cells. As colloidal gold nanoparticles are ingested by cells, the uptake enables the delivery of molecules that would not be internalized by the cells otherwise. The drug can be encapsulated in a gold core-shell particle or loaded into a larger carrier with suitable gold particles.
Therapeutic molecules may be also incorporated to the surface of gold particle. For example, a gold nanoparticle with diameter of 2 nm can incorporate 70 drug molecules (Gibson, Khanal & Zubarev 2007). This approach may be suitable for very potent drugs, but not necessarily for the less potent ones. On the other hand, gold nanoparticles do not favour drug distribution across tight tissue barriers. Suitability of gold nanoparticles in drug delivery should be investigated case by case.
Gold nanoparticles can be modified to render them more suitable for drug delivery.
They can be conjugated with ligands for over-expressed cell surface receptors to guide them into the target cells. For example, transferrin and folate receptors have been used for targeting gold nanoparticles to the cancer cells (Yang et al. 2005, Dixit et al. 2006). Glutathione-mediated release provides a strategy for intracellular release of the disulfide bridge-bound drug. This is based on the high intracellular glutathione concentration compared to its low extracellular concentration (Hong et al. 2006). However, because the number of drug molecules on the gold nanoparticle surface is limited, the approach incorporating drug directly to the nanoparticle surface is suitable mainly for applications where a low drug concentration is adequate.
Gold nanoparticles are capable of delivering large biomolecules such as peptides, proteins, and nucleic acids. Small gold nanoparticles have a high surface to volume ratio that maximizes the payload/carrier ratio, and different monolayer coatings allow the control of particle charge and hydrophobicity to maximize the delivery efficiency. Delivery can be forced, as in the case of gene guns, or achieved via cellular uptake of the particles. The gene gun method uses gold nanoparticles as bullets for the ballistic delivery of DNA (Yang et al.
1990), but it is not practical in the human gene therapy. Covalent linking of gold particles
27
with thiolated nucleic acids and non-covalent complexes with DNA provide means for cellular delivery (Oishi et al. 2006, Thomas, Klibanov 2003). Applications based on cellular delivery of proteins and peptides with gold nanoparticles have also been demonstrated (Kogan et al. 2007, Bhumkar et al. 2007). Gold nanoparticles are taken up by endocytosis, and like other nanoparticles, they face intracellular distribution problems.
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