Mimovirus Vesicle‐Based Biological Orthogonal Reaction for Cancer Diagnosis,Small Methods

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Mimovirus Vesicle‐Based Biological Orthogonal Reaction for Cancer Diagnosis
Small Methods ( IF 10.7 ) Pub Date : 2020-06-18 , DOI: 10.1002/smtd.202000291
En Ren ₁ , Chengchao Chu ₁ , Yunming Zhang ₁ , Junqing Wang ₁ , Xin Pang ₁ , Xiaoning Lin ₂ , Chao Liu ₁ , Xiaoxiao Shi ₁ , Qixuan Dai ₁ , Peng Lv ₁ , Xiaomin Wang ₂ , Xiaoyuan Chen ₃ , Gang Liu ₁

Affiliation

Herein, a tumor microenvironment (TME)‐responsive mimovirus vesicle (MVV) is engineered to deliver azide motifs (–N₃) via the membrane fusion mechanism for cancer diagnosis. As a pH‐responsive functional protein, the spike vesicular stomatitis virus G‐protein (VSVG) is genetically immobilized on surface of cell membrane vesicles. By virtue of the low‐pH activated fusogenic peculiarity of VSVG, the –N₃ groups, which are also presented on MVVs via metabolic engineering, can be directly anchored onto the target cells, thus reducing tumor heterogeneity and serving as the bait to amplify the tumor targeting of dibenzocyclooctyne‐modified diagnostic moieties. The potential diagnostic capability of such design is successfully confirmed in three different murine tumor models. Featuring excellent pH‐sensitive fusogenic traits, the developed MVVs show great responsiveness to the slightly acidic TME of solid tumors, providing a universal platform in overcoming tumor heterogeneity for precise cancer diagnosis.

中文翻译：

基于Mimovirus囊泡的生物正交反应在癌症诊断中的作用

本文中，设计了一种对肿瘤微环境（TME）响应的模拟病毒小泡（MVV），以通过膜融合机制递送叠氮基序（–N ₃）进行癌症诊断。穗状水疱性口炎病毒G蛋白（VSVG）作为一种对pH敏感的功能蛋白，通过基因固定在细胞膜囊泡表面。由于VSVG的低pH活化融合特性，–N ₃通过代谢工程也存在于MVV上的基团可以直接锚定在靶细胞上，从而降低肿瘤的异质性并充当诱饵来放大靶向二苯并环辛炔修饰的诊断部分的肿瘤。在三种不同的鼠类肿瘤模型中成功地证实了这种设计的潜在诊断能力。发达的MVV具有出色的pH敏感的融合特性，对实体瘤的微酸性TME显示出出色的响应能力，为克服肿瘤异质性提供了一个通用平台，可进行精确的癌症诊断。

更新日期：2020-06-18

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