Classical alchemists were obsessed with converting base metals into gold. A similar conundrum for cutaneous researchers is enhancing the penetration of biologically active molecules through the epidermal stratum corneum. Modern technology and chemistry allow an elegant approach to increasing penetration (Zheng et al, 2012). Alas, transmutation of lead into gold is a more difficult problem.
Zheng et al chemically modified 13 nm gold nanoparticles, and up to 120 siRNAs [small interfering RNA] were covalently attached per particle (see Rosi et al, 2006 for details and schematic figures)..The particles look like a scalp with electrically charged hairs standing on end. In addition to passing through cell membranes and modifying the biological functions of cells, the particles could penetrate through intact hairless mouse skin and human skin equivalents and retain their inhibitory function. Most remarkably, the particles could be suspended in traditional topical vehicles such as hydrated petrolatum or buffered salt solutions and highly penetrate the skin. The new technology bypasses the solvents and physical methods previously required to circumvent the stratum corneum’s barrier function.
It is exciting enough that this method will be suitable for use with siRNAs and anti-sense DNA, and the underlying concept may be modifiable for other molecules that have proven difficult to penetrate through untreated stratum corneum. The devil (a patron of alchemy) is, of course, in the details. And it is possible that there is not a special magic in the gold; but no doubt the transfer molecules will be constantly improved.
Using siRNAs with this technology may allow physicians to treat disorders of keratinization such as pachyonychia congenita and epidemolytic hyperkeratosis with highly specific molecules.
Are you ready for the new alchemy?
Zheng D, Giljohann DA, Chen DL, et al (2012) Topical delivery of siRNA-based spherical nucleic acid nanoparticle conjugates for gene regulation. PNAS 109:11975-80
Rosi NL, Giljohann Da, Thaxton CS,et al (2006) Oligonucleotide-modified gold nanoparticles for intracellular gene regulation. Science 312:1027-1030