Building bioorthogonal click-release capable artificial receptors on cancer cell surface for imaging, drug targeting and delivery.
Building bioorthogonal click-release capable artificial receptors on cancer cell surface for imaging, drug targeting and delivery.
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DOI：
10.1016/j.apsb.2022.12.018
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发表时间：
2023-06
影响因子：
14.5
通讯作者：
Wang, Wei
中科院分区：
文献类型：
--
作者：
Chen, Jing;Ji, Peng;Gnawali, Giri;Chang, Mengyang;Gao, Feng;Xu, Hang;Wang, Wei
目前的靶向给药主要依赖于癌细胞表面受体。然而，在许多情况下，蛋白质受体和归巢配体之间的结合亲和力相对较低，并且癌细胞和正常细胞之间的表达水平不显著。与传统的靶向策略不同，我们通过化学重塑细胞表面聚糖在癌细胞表面构建人工受体，开发了一种通用的癌症靶向平台。一种新的四嗪（Tz）功能化的化学受体已被设计并通过代谢聚糖工程有效地安装在癌细胞表面作为“过表达”的生物标志物。与已报道的用于药物靶向的生物缀合不同，四嗪标记的癌细胞不仅局部激活TCO笼状前药，而且通过独特的生物正交Tz-TCO点击释放反应释放活性药物。研究表明，新的药物靶向策略能够局部激活前药，最终导致有效和安全的癌症治疗。一种新的四嗪（Tz）功能化的化学受体已被设计并有效地安装在癌细胞表面作为“过表达”的生物标志物，用于靶向成像和前药活化。
The current targeting drug delivery mainly relies on cancer cell surface receptors. However, in many cases, binding affinities between protein receptors and homing ligands is relatively low and the expression level between cancer and normal cells is not significant. Distinct from conventional targeting strategies, we have developed a general cancer targeting platform by building artificial receptor on cancer cell surface via a chemical remodeling of cell surface glycans. A new tetrazine (Tz) functionalized chemical receptor has been designed and efficiently installed on cancer cell surface as “overexpressed” biomarker through a metabolic glycan engineering. Different from the reported bioconjugation for drug targeting, the tetrazine labeled cancer cells not only locally activate TCO-caged prodrugs but also release active drugs via the unique bioorthogonal Tz-TCO click-release reaction. The studies have demonstrated that the new drug targeting strategy enables local activation of prodrug, which ultimately leads to effective and safe cancer therapy. A new tetrazine (Tz) functionalized chemical receptor has been designed and efficiently installed on cancer cell surface as “overexpressed” biomarker for targeted imaging and prodrug activation.
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影响因子：
15
作者：
Blackman, Melissa L.;Royzen, Maksim;Fox, Joseph M.
通讯作者：
Fox, Joseph M.
DOI：
10.1038/s41578-020-00269-6
发表时间：
2021-04
期刊：
Nature reviews. Materials
影响因子：
--
作者：
Manzari MT;Shamay Y;Kiguchi H;Rosen N;Scaltriti M;Heller DA
通讯作者：
Heller DA
影响因子：
64.8
作者：
Hon, WC;Wilson, MI;Jones, EY
通讯作者：
Jones, EY
影响因子：
10.3
作者：
Dreher, MR;Liu, WG;Chilkoti, A
通讯作者：
Chilkoti, A
影响因子：
18.2
作者：
Devaraj NK
通讯作者：
Devaraj NK