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Eliminating blood oncogenic exosomes into the small intestine with aptamer-functionalized nanoparticles

There are disease-causing biohazards in the blood that cannot be treated with modern medicines. Here we show that an intelligently designed safe biomaterial can precisely identify, tow and dump a targeted biohazard from the blood into the small intestine. Positively charged mesoporous silica nanopar...

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Detalles Bibliográficos
Autores principales: Xie, Xiaodong, Nie, Huifang, Zhou, Yu, Lian, Shu, Mei, Hao, Lu, Yusheng, Dong, Haiyan, Li, Fengqiao, Li, Tao, Li, Bifei, Wang, Jie, Lin, Min, Wang, Chaihung, Shao, Jingwei, Gao, Yu, Chen, Jianming, Xie, Fangwei, Jia, Lee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889386/
https://www.ncbi.nlm.nih.gov/pubmed/31792209
http://dx.doi.org/10.1038/s41467-019-13316-w
Descripción
Sumario:There are disease-causing biohazards in the blood that cannot be treated with modern medicines. Here we show that an intelligently designed safe biomaterial can precisely identify, tow and dump a targeted biohazard from the blood into the small intestine. Positively charged mesoporous silica nanoparticles (MSNs) functionalized with EGFR-targeting aptamers (MSN-AP) specifically recognize and bind blood-borne negatively charged oncogenic exosomes (A-Exo), and tow A-Exo across hepatobiliary layers and Oddi’s sphincter into the small intestine. MSN-AP specifically distinguish and bind A-Exo from interfering exosomes in cell culture and rat and patient blood to form MSN-AP and A-Exo conjugates (MSN-Exo) that transverse hepatocytes, cholangiocytes, and endothelial monolayers via endocytosis and exocytosis mechanisms, although Kupffer cells have been shown to engulf some MSN-Exo. Blood MSN-AP significantly decreased circulating A-Exo levels, sequentially increased intestinal A-Exo and attenuated A-Exo-induced lung metastasis in mice. This study opens an innovative avenue to relocate blood-borne life-threatening biohazards to the intestine.