Light Control of Insulin Release and Blood Glucose Using an Injectable Photoactivated Depot

Sarode, Bhagyesh R.; Kover, Karen; Tong, Pei; Zhang, Chaoying; Friedman, Simon H.

doi:10.1021/acs.molpharmaceut.6b00633

Cited by 28 publications

(32 citation statements)

References 32 publications

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“…It has been demonstrated for several proteins that physical crosslinking to gel matrices can minimally impact biological activity, and may result in somewhat decreased activity for TEM1 released from Ru‐hydrogels (Figure S8).…”

Section: Figurementioning

confidence: 99%

“…These experiments confirmed that light exposure modulates release, enabling consistents tep-wise dosing of an active protein from Ru-hydrogelv ia light-mediated surface erosion. Because one RuAldehydel igand is exchanged, TEM1 protein released from the hydrogel wasm odified with residual ruthenium complex as Ru(bpy) 2 It has been demonstrated for several proteins that physical crosslinking to gel matrices can minimally impact biological activity, [41,42] andm ay result in somewhat decreased activity for TEM1 released from Ru-hydrogels ( Figure S8).…”

mentioning

confidence: 99%

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Ruthenium‐Crosslinked Hydrogels with Rapid, Visible‐Light Degradation

Rapp

Highley

Manor

et al. 2018

Chemistry A European J

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Incorporation of photoresponsive molecules within soft materials can provide spatiotemporal control over bulk properties and address challenges in targeted delivery and mechanical variability. However, the kinetics of in situ photochemical reactions are often slow and typically employ ultraviolet wavelengths. Here, we present a novel photoactive crosslinker Ru(bipyridine) (3-pyridinaldehyde) (RuAldehyde), which was reacted with hydrazide-functionalized hyaluronic acid to form hydrogels capable of encapsulating protein cargo. Visible light irradiation (400-500 nm) initiated rapid ligand exchange on the ruthenium center, which degraded the hydrogel within seconds to minutes, depending on gel thickness. An exemplar enzyme cargo, TEM1 β-lactamase, was loaded into and photoreleased from the Ru-hydrogel. To expand their applications, Ru-hydrogels were also processed into microgels using a microfluidic platform.

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Section: Figurementioning

confidence: 99%

mentioning

confidence: 99%

Ruthenium‐Crosslinked Hydrogels with Rapid, Visible‐Light Degradation

Rapp

Highley

Manor

et al. 2018

Chemistry A European J

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“…[133] Conjugating insulin proteins to a biodegradable insoluble matrix via a photolabile linker enabled light controlled release of insulin in an in vivo mouse model. [134] This application of light-controlled release has the potential to be applied to numerous other drugs in which spatiotemporal delivery is advantageous for treatment. While incorporation of caging groups directly into proteins has afforded investigation of many biological processes, light-responsive motifs cannot be genetically inserted into nucleic acids and thus require synthetic approaches.…”

Section: Methodsmentioning

confidence: 99%

Optochemische Steuerung biologischer Vorgänge in Zellen und Tieren

et al. 2018

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This article is protected by copyright. All rights reserved optochemical control of biology. In contrast to excellent previous reviews that focus on the chemistry of controlling biological function with light, [1] this review focuses on manipulation of cell and animal biology using photochemical approaches. Purely optogenetic approaches, not utilizing chemical operations, have been reviewed elsewhere. [2] 2. Optical control of small molecules Small molecule probes have been essential tools to perturb and control cellular processes, thereby providing an understanding of detailed biological function. Optical control of small molecule function provides an extra layer of precision to the molecular toolbox by enabling temporal and spatial control with high resolution, as discussed in the examples below. Small molecule protein dimerizers, inhibitors, metabolites, and metal ions have all been rendered lightresponsive through the chemical installation of caging groups and have been applied to the investigation of living systems. In contrast to photocaged nucleic acids, peptides, and proteins, small molecules have the added benefits of being synthetically more accessible and capable of being readily delivered into cells and animals. 2.1. Optical activation of rapamycin induced dimerization Chemical inducers of dimerization (CIDs) are prominent tools for chemical biologists to place biological processes under conditional control. [3] The most commonly utilized CID is rapamycin, which binds to FK506 binding protein (FKBP) and the FKBP-rapamycin binding domain of mTOR (FRB), forming a ternary complex. Due to the small size of FKBP and FRB, these domains have been fused to numerous proteins and subsequent heterodimerization was induced by rapamycin. Processes that have been placed under rapamycin control include Golgi/endoplasmic reticulum association to study mitosis, [4] phosphoinositide control of endocytic trafficking, [5] and inactivation of proteins by rerouting them to the mitochondria. [6] Caged rapamycin analogs allow for placement of these processes under optical control in order to enhance temporal and spatial resolution. The photocaged rapamycin analog 1 was generated through installation of a nitrobenzyl caging group at the C-40 position (Figure 1a). [7] When applied to cells, 1 still induced FKBP-FRB dimerization, indicating that the caging group alone wasn't sufficient to abrogate protein-small molecule interaction, which is consistent with previous modifications at C-40. [8] However, work by the Hahn lab had shown that a truncated FKBP, termed iFKBP, [9] exhibited increased flexibility in the loop that interacts with the C-40 position of rapamycin. This flexibility increased contacts for interaction with 1 and resulted in a distorted binding conformation that prevented formation of the ternary complex consisting of iFKBP, FRB, and 1. This system was then applied to the optical activation of FAK (focal adhesion kinase), using an engineered iFKBP-FAK fusion which rendered the kinase inactive until UV irradiation...

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“…This supposition is also supported by tissue phantom studies performed here, showing efficient light-induced de-repression at subdermal depths of as high as 1 mm, sufficient in many instances for activation within human superficial veins as well as within transcutaneous or some transepithelial disease sites. 24 Others have also demonstrated that structurally related photocages appended to solid implants can be transcutaneously photoactivated in mice, 28,29 thus we are optimistic regarding future in vivo feasibility.…”

Section: P R E P R I N T C O P Ymentioning

confidence: 99%

Optical Control of Cytokine Signaling via Bioinspired, Polymer-Induced Latency

Perdue

David

et al. 2020

Preprint

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ABSTRACTCytokine signaling is challenging to study and therapeutically exploit as the effects of these protein are often pleiotropic. A subset of cytokines can, however, exert signal specificity via association with latency-inducing proteins which cage the cytokine until disrupted by discreet biological stimuli. Inspired by this precision, here we describe a strategy for synthetic induction of cytokine latency via modification with photo-labile polymers that mimic latency while attached, then restore protein activity in response to light, thus controlling the magnitude, duration, and location of cytokine signals. We characterize the high dynamic range of latent cytokine activity modulation and find that polymer-induced latency, alone, can prolong in vivo circulation and bias receptor subunit binding. We further show that protein de-repression can be achieved with near single-cell resolution and demonstrate the feasibility of transcutaneous photoactivation. Future extensions of this approach could enable multicolor, optical reprogramming of cytokine signaling networks and more precise immunotherapies.

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Light Control of Insulin Release and Blood Glucose Using an Injectable Photoactivated Depot

Cited by 28 publications

References 32 publications

Ruthenium‐Crosslinked Hydrogels with Rapid, Visible‐Light Degradation

Ruthenium‐Crosslinked Hydrogels with Rapid, Visible‐Light Degradation

Optochemische Steuerung biologischer Vorgänge in Zellen und Tieren

Optical Control of Cytokine Signaling via Bioinspired, Polymer-Induced Latency

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