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

Optical Control of Cytokine Signaling via Bioinspired, Polymer-Induced Latency.
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DOI:
10.1021/acs.biomac.0c00264
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发表时间:
2020-07-13
期刊:
影响因子:
6.2
通讯作者:
Dreaden EC
Dreaden EC
中科院分区:
化学2区
文献类型:
--
作者:
Perdue LA;Do P;David C;Chyong A;Kellner AV;Ruggieri A;Kim HR;Salaita K;Lesinski GB;Porter CC;Dreaden EC

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Cytokine signaling is challenging to study and therapeutically exploit as the effects of these proteins are often pleiotropic. A subset of cytokines can, however, achieve 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 photolabile 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 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 derepression can be achieved with a 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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