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Delivery and Toxicity of Ruthenium Pyridine-based Nanophotoswitches in Retina

Pribisko, Melanie and Herget, Uli and Yue, Lan and Lin, Ming-yi and Chow, Robert H. and Humayun, Mark S. and Grubbs, Robert H. and Gray, Harry (2018) Delivery and Toxicity of Ruthenium Pyridine-based Nanophotoswitches in Retina. Investigative Ophthalmology and Visual Science, 59 (9). Art. No. 232. ISSN 0146-0404.

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Purpose : Nanophotoswitches (NPSs) offer a new tool for optical stimulation of neuronal activity, in vitro and potentially in vivo. Our group previously reported a ruthenium bipyridine (Rubpy)-based NPS (Rubpy-C17) that, after injection into the eyes of photoreceptor degenerated blind rats, elicited electrical activity in the contralateral superior colliculus upon light illumination. We wish to optimize delivery, efficacy and biosafety of the NPSs; our preliminary experiments examining the Rubpy complexes in vivo suggest low acute toxicity. Intravitreal delivery of the Rubpy-C17 complexes has been shown to restore light response recorded from the superior colliculus of the photoreceptor degenerate RCS rats 1 day after the injection. The restored light response was largely preserved 3 days after the injection, suggesting that the Rubpy-C17 complexes are well tolerated by the retinal neurons during the test period. Methods : Promising NPSs molecules absorb and can be visualized by their luminescence upon visible wavelength illumination. This enables us to evaluate the toxicity of the NPSs using an array of in vitro, in vivo and ex vivo tests, including in vitro electrochemical and spectroscopic studies to determine DNA binding and DNA intercalation. In addition, the NPSs were embedded in polymer matrices and the emission monitored to determine the rate of release upon injection into the eye. Results : Preliminary data show that young zebrafish tolerate injection of up to 100 uM Rubpy-C17 into the eye, with complete disappearance of the Rubpy-C17 emission from the eye within a day. Interestingly, blue-green emission appears in the liver region as the orange-red emission of Rubpy-C17 decreases. As this may be a result of metabolism of the Rubpy-C17, we extracted the blue-green emitting molecule for characterization. Initial studies of slow-release drug delivery system and conditions indicate some success with polyethyleneglycol-poly(lactic-co-glycolic acid)-poly-L-lysine (PEG-PLGA-PEG) and polycaprolactone (PCL) polymers. Conclusions : Our data suggest that NPSs dissolved in a DMSO solution and intravitreally administered remain stable and active in the ocular environment up to at least one day post injection, which can be extended when coadministered with certain polymer mixtures. The DNA binding and DNA intercalation studies, in combination with the extended release polymers, address toxicity concerns of the NPSs in the eye.

Item Type:Article
Related URLs:
URLURL TypeDescription
Herget, Uli0000-0002-4419-1414
Humayun, Mark S.0000-0002-5830-5208
Grubbs, Robert H.0000-0002-0057-7817
Gray, Harry0000-0002-7937-7876
Additional Information:© 2018 This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. Commercial Relationships: Melanie Pribisko, None; Uli Herget, None; Lan Yue, None; Ming-yi Lin, None; Robert Chow, None; Mark Humayun, None; Robert Grubbs, None; Harry Gray, None. Support: NSF AIRTT.
Funding AgencyGrant Number
Issue or Number:9
Record Number:CaltechAUTHORS:20180926-125050352
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Official Citation:Melanie Pribisko, Uli Herget, Lan Yue, Ming-yi Lin, Robert H Chow, Mark S. Humayun, Robert H Grubbs, Harry Gray; Delivery and Toxicity of Ruthenium Pyridine-based Nanophotoswitches in Retina. Invest. Ophthalmol. Vis. Sci. 2018;59(9):232
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:89961
Deposited By: Tony Diaz
Deposited On:26 Sep 2018 21:36
Last Modified:09 Mar 2020 13:18

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