In Situ Self-Assembled Nanofibers Precisely Target Cancer-Associated Fibroblasts for Improved Tumor Imaging

Xiao Xiao Zhao; Li Li Li; Ying Zhao; Hong Wei An; Qian Cai; Jia Yan Lang; Xue Xiang Han; Bo Peng; Yue Fei; Hao Liu; Hao Qin; Guangjun Nie; Hao Wang

doi:10.1002/anie.201908185

In Situ Self-Assembled Nanofibers Precisely Target Cancer-Associated Fibroblasts for Improved Tumor Imaging

Xiao Xiao Zhao, Li Li Li, Ying Zhao, Hong Wei An, Qian Cai, Jia Yan Lang, Xue Xiang Han, Bo Peng, Yue Fei, Hao Liu, Hao Qin, Guangjun Nie, Hao Wang

Houston Methodist

Research output: Contribution to journal › Article › peer-review

120 Scopus citations

Abstract

Tumor complexity makes the development of highly sensitive tumor imaging probes an arduous task. Here, we construct a peptide-based near-infrared probe that is responsive to fibroblast activation protein-α (FAP-α), and specifically forms nanofibers on the surface of cancer-associated fibroblasts (CAFs) in situ. The assembly/aggregation-induced retention (AIR) effect results in enhanced accumulation and retention of the probe around the tumor, resulting in a 5.5-fold signal enhancement in the tumor 48 h after administration compared to that of a control molecule that does not aggregate. The probe provides a prolonged detectable window of 48 h for tumor diagnosis. The selective assembly of the probe results in a signal intensity over four- and fivefold higher in tumor than in the liver and kidney, respectively. With enhanced tumor imaging capability, this probe can visualize small tumors around 2 mm in diameter.

Original language	English (US)
Pages (from-to)	15287-15294
Number of pages	8
Journal	Angewandte Chemie - International Edition
Volume	58
Issue number	43
DOIs	https://doi.org/10.1002/anie.201908185
State	Published - Oct 21 2019

Keywords

cancer-associated fibroblasts
cyanine
peptides
self-assembly
tumor imaging

ASJC Scopus subject areas

Catalysis
General Chemistry

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10.1002/anie.201908185

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title = "In Situ Self-Assembled Nanofibers Precisely Target Cancer-Associated Fibroblasts for Improved Tumor Imaging",

abstract = "Tumor complexity makes the development of highly sensitive tumor imaging probes an arduous task. Here, we construct a peptide-based near-infrared probe that is responsive to fibroblast activation protein-α (FAP-α), and specifically forms nanofibers on the surface of cancer-associated fibroblasts (CAFs) in situ. The assembly/aggregation-induced retention (AIR) effect results in enhanced accumulation and retention of the probe around the tumor, resulting in a 5.5-fold signal enhancement in the tumor 48 h after administration compared to that of a control molecule that does not aggregate. The probe provides a prolonged detectable window of 48 h for tumor diagnosis. The selective assembly of the probe results in a signal intensity over four- and fivefold higher in tumor than in the liver and kidney, respectively. With enhanced tumor imaging capability, this probe can visualize small tumors around 2 mm in diameter.",

keywords = "cancer-associated fibroblasts, cyanine, peptides, self-assembly, tumor imaging",

author = "Zhao, {Xiao Xiao} and Li, {Li Li} and Ying Zhao and An, {Hong Wei} and Qian Cai and Lang, {Jia Yan} and Han, {Xue Xiang} and Bo Peng and Yue Fei and Hao Liu and Hao Qin and Guangjun Nie and Hao Wang",

note = "Funding Information: This work was supported by the National Natural Science Foundation of China (31671028, 51873045, 51725302, 51573032, and 11621505), and Key Project of Chinese Academy of Sciences (QYZDJ-SSW-SLH022 and GJHZ1541). H.W. thanks the CAS Interdisciplinary Innovation Team. L.-L.L. thanks the Youth Innovation Promotion, CAS (2017053). We are very grateful to Bogdan Cristinoi (Copenhagen University, Denmark) for helping with the revised manuscript. Publisher Copyright: {\textcopyright} 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim",

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doi = "10.1002/anie.201908185",

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T1 - In Situ Self-Assembled Nanofibers Precisely Target Cancer-Associated Fibroblasts for Improved Tumor Imaging

AU - Zhao, Xiao Xiao

AU - Li, Li Li

AU - Zhao, Ying

AU - An, Hong Wei

AU - Cai, Qian

AU - Lang, Jia Yan

AU - Han, Xue Xiang

AU - Peng, Bo

AU - Fei, Yue

AU - Liu, Hao

AU - Qin, Hao

AU - Nie, Guangjun

AU - Wang, Hao

N1 - Funding Information: This work was supported by the National Natural Science Foundation of China (31671028, 51873045, 51725302, 51573032, and 11621505), and Key Project of Chinese Academy of Sciences (QYZDJ-SSW-SLH022 and GJHZ1541). H.W. thanks the CAS Interdisciplinary Innovation Team. L.-L.L. thanks the Youth Innovation Promotion, CAS (2017053). We are very grateful to Bogdan Cristinoi (Copenhagen University, Denmark) for helping with the revised manuscript. Publisher Copyright: © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

PY - 2019/10/21

Y1 - 2019/10/21

N2 - Tumor complexity makes the development of highly sensitive tumor imaging probes an arduous task. Here, we construct a peptide-based near-infrared probe that is responsive to fibroblast activation protein-α (FAP-α), and specifically forms nanofibers on the surface of cancer-associated fibroblasts (CAFs) in situ. The assembly/aggregation-induced retention (AIR) effect results in enhanced accumulation and retention of the probe around the tumor, resulting in a 5.5-fold signal enhancement in the tumor 48 h after administration compared to that of a control molecule that does not aggregate. The probe provides a prolonged detectable window of 48 h for tumor diagnosis. The selective assembly of the probe results in a signal intensity over four- and fivefold higher in tumor than in the liver and kidney, respectively. With enhanced tumor imaging capability, this probe can visualize small tumors around 2 mm in diameter.

AB - Tumor complexity makes the development of highly sensitive tumor imaging probes an arduous task. Here, we construct a peptide-based near-infrared probe that is responsive to fibroblast activation protein-α (FAP-α), and specifically forms nanofibers on the surface of cancer-associated fibroblasts (CAFs) in situ. The assembly/aggregation-induced retention (AIR) effect results in enhanced accumulation and retention of the probe around the tumor, resulting in a 5.5-fold signal enhancement in the tumor 48 h after administration compared to that of a control molecule that does not aggregate. The probe provides a prolonged detectable window of 48 h for tumor diagnosis. The selective assembly of the probe results in a signal intensity over four- and fivefold higher in tumor than in the liver and kidney, respectively. With enhanced tumor imaging capability, this probe can visualize small tumors around 2 mm in diameter.

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In Situ Self-Assembled Nanofibers Precisely Target Cancer-Associated Fibroblasts for Improved Tumor Imaging

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Keywords

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