Engineering a HEK-293T exosome-based delivery platform for efficient tumor-targeting chemotherapy/internal irradiation combination therapy.
Engineering a HEK-293T exosome-based delivery platform for efficient tumor-targeting chemotherapy/internal irradiation combination therapy.
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DOI：
10.1186/s12951-022-01462-1
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发表时间：
2022-05-31
影响因子：
10.2
通讯作者：
Zhang, Ruiguo
中科院分区：
文献类型：
--
作者：
Wang, Congcong;Li, Ning;Li, Yutian;Hou, Shasha;Zhang, Wenxin;Meng, Zhaowei;Wang, Shen;Jia, Qiang;Tan, Jian;Wang, Renfei;Zhang, Ruiguo
关键词：
外来体是由哺乳动物细胞主动内源性分泌的纳米级单层膜囊泡。目前，具有肿瘤靶向成像和治疗潜力的多功能外泌体在癌症研究中引起了广泛的兴趣。在本文中，我们通过工程化HEK-293 T细胞以表达融合至αv整联蛋白特异性iRGD肽和酪氨酸片段的充分表征的外泌体膜蛋白（Lamp 2b），开发了基于外泌体的多功能靶向递送平台。该平台装载有多柔比星（Dox），并使用氯胺-T方法用放射性碘-131（131 I）标记。体外共聚焦成像和流式细胞术证明iRGD外泌体对整合素αvβ3阳性未分化甲状腺癌（ATC）细胞具有高效靶向和Dox递送，体内131 I标记后，单光子发射计算机断层扫描-计算机断层扫描证实了其出色的肿瘤靶向能力。此外，静脉注射该载体将Dox和131 I特异性地递送至肿瘤组织，导致8505 C异种移植小鼠模型中显著的肿瘤生长抑制，同时显示出生物安全性且无副作用。这些开发的多功能外泌体（表示为Dox@iRGD-Exos-131 I）为ATC的当前治疗提供了新的见解，并具有提高对广泛整合素αvβ3过表达肿瘤的治疗疗效的巨大潜力。在线版本包含补充材料，可通过10.1186/s12951-022-01462-1获得。
Exosomes are nanoscale monolayer membrane vesicles that are actively endogenously secreted by mammalian cells. Currently, multifunctional exosomes with tumor-targeted imaging and therapeutic potential have aroused widespread interest in cancer research. Herein, we developed a multifunctional HEK-293T exosome-based targeted delivery platform by engineering HEK-293T cells to express a well-characterized exosomal membrane protein (Lamp2b) fused to the αv integrin-specific iRGD peptide and tyrosine fragments. This platform was loaded with doxorubicin (Dox) and labeled with radioiodine-131 (131I) using the chloramine-T method. iRGD exosomes showed highly efficient targeting and Dox delivery to integrin αvβ3-positive anaplastic thyroid carcinoma (ATC) cells as demonstrated by confocal imaging and flow cytometry in vitro and an excellent tumor-targeting capacity confirmed by single-photon emission computed tomography-computed tomography after labeling with 131I in vivo. In addition, intravenous injection of this vehicle delivered Dox and 131I specifically to tumor tissues, leading to significant tumor growth inhibition in an 8505C xenograft mouse model, while showing biosafety and no side effects. These as-developed multifunctional exosomes (denoted as Dox@iRGD-Exos-131I) provide novel insight into the current treatment of ATC and hold great potential for improving therapeutic efficacy against a wide range of integrin αvβ3-overexpressing tumors. The online version contains supplementary material available at 10.1186/s12951-022-01462-1.
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影响因子：
5.6
作者：
Gangadaran P;Hong CM;Oh JM;Rajendran RL;Kalimuthu S;Son SH;Gopal A;Zhu L;Baek SH;Jeong SY;Lee SW;Lee J;Ahn BC
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影响因子：
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作者：
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影响因子：
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DOI：
10.1002/exp.20210171
发表时间：
2022-02
期刊：
Exploration (Beijing, China)
影响因子：
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作者：
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影响因子：
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作者：
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