Photoactivated, localized drug delivery utilizing visible and infrared light

Light is a powerful pharmacological tool that can be used to selectively activate a photo-reactive drug in a specific location. This method, called photodynamic therapy, has been used successfully as a treatment for a variety of cancers including lung, pancreatic, esophageal, and skin cancers. However, most current photodynamic therapies require ultra-violet light, which has poor tissue penetration depths and can severely damage cells. This technology is a class of ruthenium-based tethers that can bind compounds and release them when exposed to visible or infrared light. It can be used to deliver a variety of biologically active molecules, including neurotransmitters, locally and selectively.

Cost-effective and biocompatible visible light allows for localized delivery with single-cell precision

In addition to being far more biocompatible and having longer penetration depths, visible and infrared light sources are also far more cost effective than high-energy ultraviolet light. This technology relies on the unique photoactivity of ruthenium-bipyridal complexes, whose structures change dramatically upon activation with low-energy visible and, in some cases, infrared light. These ruthenium-tethers can potentially be used in combination with any molecule that contains an amino functionality that is required for its bioactivity.

This technology has been demonstrated on a number of tether-neurotransmitter complexes, and it has been utilized in vivo to map receptors for the neurotransmitter GABA. It has also been used to photoactivate neurons and dendritic spines with single-cell precision.

Lead Inventor:

Rafael Yuste, M.D., Ph.D.

Applications:

• Selective release of chemotherapeutic agents
• Selective release of neurotransmitters
• Selective delivery of a variety of bioactive compounds
• Basic research tool for imaging and cell labeling

Advantages:

• Visible and infrared light pose no risk to biological tissues
• Visible and infrared light sources are inexpensive when compared to ultraviolet light sources
• Allows for precise control over drug delivery
• Can be adapted for a wide range of drug-tether complexes

Patent Information:

Patent Issued

Tech Ventures Reference: IR M09-102

Related Publications:

• Fino E, Araya R, Peterka DS, Salierno M, Etchenique R, and Yuste R. "RuBi-Glutamate: two-photon and visible-light photoactivation of neurons and dendritic spines" Front. Neural Circuits, 2009 27 May;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 Apr;104(4):418-22.

• Zayat L, Calero C, Alborés P, Baraldo L, Etchenique R. "A new strategy for neurochemical photodelivery: metal-ligand heterolytic cleavage." J Am Chem Soc. 2003 Jan 29;125(4):882-3.

• Rial Verde EM1, Zayat L, Etchenique R, Yuste R. "Photorelease of GABA with Visible Light Using an Inorganic Caging Group." Front Neural Circuits. 2008 Aug 13;2:2.

• Zayat L1, Salierno M, Etchenique R. "Ruthenium(II) bipyridyl complexes as photolabile caging groups for amines." Inorg Chem. 2006 Feb 20;45(4):1728-31.