The expanding role of split protein complementation in opsin-free optogenetics

Skeeters, Savanna S.; Camp, Tyler; Fan, Huaxun; Zhang, Kai

doi:10.1016/j.coph.2022.102236

Cited by 2 publications

(1 citation statement)

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“…Moreover, light can be focused onto a region of interest to afford remarkable spatiotemporal control. This is especially the case in the context of fluorescent- and photoacoustic-based imaging studies, − optogenetic stimulation, , light-activatable analyte donor systems, − and photodynamic therapy (PDT) or photothermal therapy (PTT) . With regards to the latter two applications, we envision existing laser and LED systems used in humans can also be compatible with the NIR-nanogel technology, highlighting its translational potential.…”

Section: Discussionmentioning

confidence: 99%

Repurposing Cyanine Photoinstability To Develop Near-Infrared Light-Activatable Nanogels for In Vivo Cargo Delivery

et al. 2022

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The favorable properties of cyanines (e.g., nearinfrared (NIR) absorbance and emission) have made this class of dyes popular for a wide variety of biomedical applications. However, many cyanines are prone to rapid photobleaching when irradiated with light. In this study, we have exploited this undesirable trait to develop NIR-nanogels for NIR light-mediated cargo delivery. NIR-nanogels feature a photolabile cyanine crosslinker (Cy780-Acryl) that can cleave via dioxetane chemistry when irradiated. This photochemical process results in the formation of two carbonyl fragments and concomitant NIR-nanogel degradation to facilitate cargo release. In contrast to studies where cyanines are utilized as photocages, our approach does not require direct chemical attachment to the cargo, thus expanding our ability to deliver molecules that cannot be covalently modified. We showcase this feature by encapsulating a palette of small-molecule chemotherapeutics that feature a structurally diverse chemical architecture. To demonstrate site-selective release in vivo, we generated a murine model of breast cancer. Relative to nonlight irradiated and drugfree controls, treatment with NIR-nanogels loaded with paclitaxel (a potent cytotoxic agent) and NIR light resulted in significant attenuation of tumor growth. Moreover, we show via histological staining of the vital organs that minimal off-target effects are observed.

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