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

Xiaodong Xie, Huifang Nie, Yu Zhou, Shu Lian, Hao Mei, Yusheng Lu, Haiyan Dong, Fengqiao Li, Tao Li, Bifei Li, Jie Wang, Min Lin, Chaihung Wang, Jingwei Shao, Yu Gao, Jianming Chen, Fangwei Xie and Lee Jia ()
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Xiaodong Xie: Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Minjiang University
Huifang Nie: Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Minjiang University
Yu Zhou: Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Minjiang University
Shu Lian: Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Minjiang University
Hao Mei: Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Minjiang University
Yusheng Lu: Institute of Oceanography, Minjiang University
Haiyan Dong: Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Minjiang University
Fengqiao Li: Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Minjiang University
Tao Li: Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Minjiang University
Bifei Li: Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Minjiang University
Jie Wang: Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Minjiang University
Min Lin: Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Minjiang University
Chaihung Wang: Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Minjiang University
Jingwei Shao: Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Minjiang University
Yu Gao: Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Minjiang University
Jianming Chen: Institute of Oceanography, Minjiang University
Fangwei Xie: Department of Oncology, Fuzhou General Hospital
Lee Jia: Cancer Metastasis Alert and Prevention Center, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Minjiang University

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-13316-w

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