Selective thrombosis of tumor for enhanced hypoxia-activated prodrug therapy

One of the main challenges for tumor vascular infarction in combating cancer lies in failing to produce sustained complete thrombosis. Inspired by the capability of vascular infarction in blocking the delivery of oxygen to aggravate tumor hypoxia, we herein present the performance of selective tumor...

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Main Authors: Ma, Zhaoyu, Zhang, Yifan, Dai, Xinxin, Zhang, Weiyun, Mohamed F. Foda, Zhang, Jin, Zhao, Yanli, Han, Heyou
Other Authors: School of Physical and Mathematical Sciences
Format: Article
Language:English
Published: 2022
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Online Access:https://hdl.handle.net/10356/155941
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1559412023-02-28T19:27:12Z Selective thrombosis of tumor for enhanced hypoxia-activated prodrug therapy Ma, Zhaoyu Zhang, Yifan Dai, Xinxin Zhang, Weiyun Mohamed F. Foda Zhang, Jin Zhao, Yanli Han, Heyou School of Physical and Mathematical Sciences Science::Chemistry Cancer Treatment Metal–Organic Framework One of the main challenges for tumor vascular infarction in combating cancer lies in failing to produce sustained complete thrombosis. Inspired by the capability of vascular infarction in blocking the delivery of oxygen to aggravate tumor hypoxia, we herein present the performance of selective tumor thrombus inducing hypoxia activation therapy to improve the therapeutic index of coagulation-based tumor therapy. By encapsulating coagulation-inducing protease thrombin and a hypoxia-activated prodrug (HAP) tirapazamine into metal-organic framework nanoparticles with a tumor-homing ligand, the obtained nanoplatform selectively activates the platelet aggregation at tumor to induce the thrombosis and vascular obstruction therapy by the exposed thrombin. Meanwhile, the thrombus can cut off the blood oxygen supply and potentiate the hypoxia levels to enhance the HAP therapy. This strategy not only addresses the dissatisfaction of vascular therapy, but also conquers the dilemma of inadequate hypoxia in the HAP treatment. Since clinical operations such as surgery can be used to induce the coagulation, the coagulation based synergistic therapy is promising to be translated into a clinical combination regimen. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) Submitted/Accepted version This work was supported by grants from the National Natural Science Foundation of China (21778020, 31750110464, and 31950410755), the Sci-Tech Innovation Foundation of Huazhong Agricultural University (2662018PY024), the National Key R&D Program of China (2016YFD0500706), and the Science and Technology Major Project of Guangxi (Gui Ke AA18118046). This work was also supported by the Singapore Agency for Science, Technology and Research (A*STAR) AME IRG grant (A20E5c0081), and the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03). 2022-03-25T01:59:23Z 2022-03-25T01:59:23Z 2021 Journal Article Ma, Z., Zhang, Y., Dai, X., Zhang, W., Mohamed F. Foda, Zhang, J., Zhao, Y. & Han, H. (2021). Selective thrombosis of tumor for enhanced hypoxia-activated prodrug therapy. Advanced Materials, 33(41), 2104504-. https://dx.doi.org/10.1002/adma.202104504 0935-9648 https://hdl.handle.net/10356/155941 10.1002/adma.202104504 41 33 2104504 en A20E5c0081 NRF-NRFI2018-03 Advanced Materials This is the peer reviewed version of the following article: Ma, Z., Zhang, Y., Dai, X., Zhang, W., Mohamed F. Foda, Zhang, J., Zhao, Y. & Han, H. (2021). Selective thrombosis of tumor for enhanced hypoxia-activated prodrug therapy. Advanced Materials, 33(41), 2104504, which has been published in final form at https://doi.org/10.1002/adma.202104504. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Chemistry
Cancer Treatment
Metal–Organic Framework
spellingShingle Science::Chemistry
Cancer Treatment
Metal–Organic Framework
Ma, Zhaoyu
Zhang, Yifan
Dai, Xinxin
Zhang, Weiyun
Mohamed F. Foda
Zhang, Jin
Zhao, Yanli
Han, Heyou
Selective thrombosis of tumor for enhanced hypoxia-activated prodrug therapy
description One of the main challenges for tumor vascular infarction in combating cancer lies in failing to produce sustained complete thrombosis. Inspired by the capability of vascular infarction in blocking the delivery of oxygen to aggravate tumor hypoxia, we herein present the performance of selective tumor thrombus inducing hypoxia activation therapy to improve the therapeutic index of coagulation-based tumor therapy. By encapsulating coagulation-inducing protease thrombin and a hypoxia-activated prodrug (HAP) tirapazamine into metal-organic framework nanoparticles with a tumor-homing ligand, the obtained nanoplatform selectively activates the platelet aggregation at tumor to induce the thrombosis and vascular obstruction therapy by the exposed thrombin. Meanwhile, the thrombus can cut off the blood oxygen supply and potentiate the hypoxia levels to enhance the HAP therapy. This strategy not only addresses the dissatisfaction of vascular therapy, but also conquers the dilemma of inadequate hypoxia in the HAP treatment. Since clinical operations such as surgery can be used to induce the coagulation, the coagulation based synergistic therapy is promising to be translated into a clinical combination regimen.
author2 School of Physical and Mathematical Sciences
author_facet School of Physical and Mathematical Sciences
Ma, Zhaoyu
Zhang, Yifan
Dai, Xinxin
Zhang, Weiyun
Mohamed F. Foda
Zhang, Jin
Zhao, Yanli
Han, Heyou
format Article
author Ma, Zhaoyu
Zhang, Yifan
Dai, Xinxin
Zhang, Weiyun
Mohamed F. Foda
Zhang, Jin
Zhao, Yanli
Han, Heyou
author_sort Ma, Zhaoyu
title Selective thrombosis of tumor for enhanced hypoxia-activated prodrug therapy
title_short Selective thrombosis of tumor for enhanced hypoxia-activated prodrug therapy
title_full Selective thrombosis of tumor for enhanced hypoxia-activated prodrug therapy
title_fullStr Selective thrombosis of tumor for enhanced hypoxia-activated prodrug therapy
title_full_unstemmed Selective thrombosis of tumor for enhanced hypoxia-activated prodrug therapy
title_sort selective thrombosis of tumor for enhanced hypoxia-activated prodrug therapy
publishDate 2022
url https://hdl.handle.net/10356/155941
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