Repurposing Cyanine Photoinstability To Develop Near-Infrared Light-Activatable Nanogels for In Vivo Cargo Delivery.
Repurposing Cyanine Photoinstability To Develop Near-Infrared Light-Activatable Nanogels for In Vivo Cargo Delivery.
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DOI：
10.1021/jacs.2c08187
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发表时间：
2022-10-05
影响因子：
15
通讯作者：
Chan, Jefferson
中科院分区：
文献类型：
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作者：
Hernandez, Rodrigo Tapia;Lee, Michael C.;Yadav, Anuj K.;Chan, Jefferson
花青的有利性质（例如，近红外（NIR）吸收和发射）已经使得这类染料广泛用于各种生物医学应用。然而，许多花菁在光照下容易发生快速光漂白。在这项研究中，我们利用这种不受欢迎的特性来开发用于NIR光介导的货物递送的NIR纳米凝胶。NIR-纳米凝胶具有光不稳定的花青交联剂（Cy 780-Acryl），其可以在照射时通过二氧杂环丁烷化学裂解。该光化学过程导致两个羰基片段的形成和伴随的NIR-纳米凝胶降解以促进货物释放。与利用花青作为光笼的研究相反，我们的方法不需要与货物直接化学连接，从而扩大了我们递送不能共价修饰的分子的能力。我们通过封装具有结构多样的化学结构的小分子化疗药物来展示这一特征。为了证明在体内的位点选择性释放，我们产生了乳腺癌的小鼠模型。相对于非光照射和无药物对照，用装载有紫杉醇（一种有效的细胞毒性剂）和NIR光的NIR纳米凝胶治疗导致肿瘤生长的显著衰减。此外，我们通过重要器官的组织学染色显示，观察到最小的脱靶效应。
The favorable properties of cyanines (e.g., near-infrared (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 cross-linker (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 drug-free 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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影响因子：
18.3
作者：
Knox HJ;Chan J
通讯作者：
Chan J
影响因子：
23.5
作者：
Friedman HC;Cosco ED;Atallah TL;Jia S;Sletten EM;Caram JR
通讯作者：
Caram JR
与激发激光器相匹配的短波红外多胸荧光团可实时实时非侵入性，多色在体内成像。
影响因子：
21.8
作者：
Cosco ED;Spearman AL;Ramakrishnan S;Lingg JGP;Saccomano M;Pengshung M;Arús BA;Wong KCY;Glasl S;Ntziachristos V;Warmer M;McLaughlin RR;Bruns OT;Sletten EM
通讯作者：
Sletten EM
DOI：
10.1002/anie.202003687
发表时间：
2021-03-01
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Gardner SH;Reinhardt CJ;Chan J
通讯作者：
Chan J
影响因子：
21.8
作者：
通讯作者：
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