Controlled localized and rapid delivery of natural or synthetic biomolecules is desirable for the treatment of a number of conditions, such as nervous system disorders, tumors and cardiovascular diseases. To control the release of bioactive compounds, these biomolecules are often "caged" or rendered biologically inert through the attachment of a protecting photolabile group. Light can then be used to "uncage" or cleave the molecule, thus activating it. However, commercially available methods for uncaging molecules often require ultraviolet (UV) light, which require expensive equipment and cause damage to cells, tissues and organs. This technology presents a novel family of photolabile compounds that can be used with visible light for delivery of biomolecules.
Uncaging of biomolecules with visible light provides high temporal and spatial release control
Visible light photorelease has many advantages over UV light photorelease, including decreased scattering and deeper tissue penetration. By using a transition metal, ruthenium, as the photosensor, these new caging compounds are responsive to a number of light sources, including visible light and IR light, after one and two-photon excitation. Since a metal (M)-organic molecule bond is typically weaker than a covalent σ bond, the ruthenium cage can be broken using lower irradiation energy. Because of this, the ruthenium-based cages are also able to deliver compounds at much faster timescales (nanoseconds) with increased uncaging yields than traditional caged compounds.
These compounds have been used for the successful photorelease of many active biomolecules, such as GABA, glutamate, dopamine, nicotine, in neurons in vitro and in vivo using visible light, IR light with LED, arc lamps or lasers.
Lead Inventor:
Applications:
- Localized drug delivery to patients for treatment of nervous system disorders, tumors or cardiovascular disease
- Light controlled drug release using photo-optic devices, probes or fibers
- Drug discovery experiments to determine the effect of biomolecule on a biological sample, such a tissue sample
Advantages:
- Photorelease initiated by any visible or infrared light including LEDs, lasers, and light from microscopes (including one- and two-photon light)
- Visible light is not damaging to cells, making it beneficial for clinical applications
Patent Information:
Tech Ventures Reference: IR M04-31
Related Publications:
- Nikolenko V, Yuste R. Zayat L, Baraldo LM, Etchenique R. "Two photon uncaging of neurochemicals using inorganic metal complexes" Chem Commmun., 2005 February 7: 13: 17252-54.
- Verde EMR, Zayat L, Etchenique R, Yuste, R. "Photorelease of GABA with visibile light using an inorganic caging group" Front Neural Circuits. 2008 Aug 13:2(2).
- Fino E, Araya R, Peterka DS, Salierno M, Etchenique R, Yuste R. "RuBi-Glutamate: two-photon and visible light photoactivation of neurons and dendritic spines" Front Neural Circuits. 2009 May 27: 3:2.
- Salierno M, Marceca E, Peterka DS, Yuste R, Etchenique R. "A fast ruthenium polypyridine cage complex photoreleases glutamate with visible or IR light in one and two photon regimes" J Inorg Biochem. 2010 Oct 1: 104(4):418-422.