News from the Martinez’ research group: Porous silicon nanoparticles:
Porous silicon is a wonderful material that can be used for a variety of applications in electronics, optics, and biomedicine. It works well as solar cells, batteries, sensors, or drug delivery devices because of its unique features: semiconductor material; light-emitting properties; large surface area in small volume; tunable pore size; and convenient surface modification. In addition, it is also biodegradable and non-toxic, which is important for medical applications.
Porous silicon can be made through electrochemical etching of a silicon wafer using hydrofluoric acid in ethanol. The etching occurs in the direction of the current and results in irregular pores aligned in the same direction. The pore dimensions and material size can be tuned by adjusting the settings of the etch, especially the current density is of importance. Depending on the pore size (pore diameter and pore wall thickness), porous silicon can function as a diagnostic and/or therapeutic tool. Thin pore walls result in luminescent properties that can be used for monitoring location, concentration, and degradation. Pore size and surface modifications affect drug loading, binding, and delivery.
Maria Teresa Bezem, a PhD candidate from the Biorecognition group at the University of Bergen, visited the lab of Michael J. Sailor at the University of California, San Diego, to synthesize porous silicon nanoparticles. Back in Bergen, she investigated the loading of a protein drug called tyrosine hydroxylase (TH) which has been the focus of her PhD thesis.
Proteins are macromolecules carrying out a diversity of biological tasks, such as signaling, transport, enzyme catalysis, structural rigidity etc. In disease states, protein levels and function might be altered, and the disease itself could be caused by the lack or malfunctioning of one specific protein. It can therefore be beneficial for a patient to be treated with a so-called protein replacement therapy. Such therapeutic proteins, also called biologics, are in fact an emerging type of drugs now topping the lists of best-selling medicines (with regards to revenue).
The protein TH is an enzyme that catalyzes the first and rate-limiting step in the synthesis of dopamine, a neurotransmitter used as a signaling molecule in the nervous system for movement, cognition, and digestion. In diseases where levels of TH and dopamine are low, such as Parkinson’s disease and a rare genetic disorder called TH deficiency, therapeutic delivery of TH is expected to increase these levels and thereby restore, at least partially, normal function of the nervous system. TH is however a large and complex protein, which needs to function inside neurons and cannot just be given into the blood, as other therapeutic proteins.
Loading TH into a porous silicon nanoparticle, ensures that TH is stabilized and protected from degradation while being delivered to neurons. In this way, the nanoparticle is the vehicle that carries TH, the cargo. In order to develop such a treatment based on enzyme substitution, it is necessary to know: which nanoparticle properties and loading conditions are optimal; and how the interaction between the TH protein and the porous silicon nanoparticle affects the binding and function. This depends on: the chemical groups on the outer surfaces of the protein and the nanoparticle; and the physical laws of the forces exerted between the two. The ultimate goal would be to administer as much of highly active TH as necessary, with as few vehicles as possible.
Bezem and collaborators (Johannessen FG, Kråkenes TA, Sailor MJ and Martinez A) recently published an article in Molecular Pharmaceutics where they explain how they found that local electrostatic attraction dominates in the binding of TH in porous silicon nanoparticles. For further reading, please see article in Molecular Pharmaceutics.