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Engineering liquid metal-based nanozyme for enhancing microwave dynamic therapy in breast cancer PDX model

BACKGROUNDS: The novel concept of microwave dynamic therapy (MDT) solves the problem of incomplete tumor eradication caused by non-selective heating and uneven temperature distribution of microwave thermal therapy (MWTT) in clinic, but the poor delivery of microwave sensitizer and the obstacle of tu...

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Autores principales: Wu, Qiong, Yu, Yongnian, Yu, Xiaorui, Du, Qijun, Gou, Li, Tan, Longfei, Fu, Changhui, Ren, Xiangling, Ren, Jun, Xiao, Kai, Meng, Xianwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617232/
https://www.ncbi.nlm.nih.gov/pubmed/37904235
http://dx.doi.org/10.1186/s12951-023-02121-9
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author Wu, Qiong
Yu, Yongnian
Yu, Xiaorui
Du, Qijun
Gou, Li
Tan, Longfei
Fu, Changhui
Ren, Xiangling
Ren, Jun
Xiao, Kai
Meng, Xianwei
author_facet Wu, Qiong
Yu, Yongnian
Yu, Xiaorui
Du, Qijun
Gou, Li
Tan, Longfei
Fu, Changhui
Ren, Xiangling
Ren, Jun
Xiao, Kai
Meng, Xianwei
author_sort Wu, Qiong
collection PubMed
description BACKGROUNDS: The novel concept of microwave dynamic therapy (MDT) solves the problem of incomplete tumor eradication caused by non-selective heating and uneven temperature distribution of microwave thermal therapy (MWTT) in clinic, but the poor delivery of microwave sensitizer and the obstacle of tumor hypoxic microenvironment limit the effectiveness of MDT. RESULTS: Herein, we engineer a liquid metal-based nanozyme LM@ZIF@HA (LZH) with eutectic Gallium Indium (EGaIn) as the core, which is coated with CoNi-bimetallic zeolite imidazole framework (ZIF) and hyaluronic acid (HA). The flexibility of the liquid metal and the targeting of HA enable the nanozyme to be effectively endocytosed by tumor cells, solving the problem of poor delivery of microwave sensitizers. Due to the catalase-like activity, the nanozyme catalyze excess H(2)O(2) in the tumor microenvironment to generate O(2), alleviating the restriction of the tumor hypoxic microenvironment and promoting the production of ROS under microwave irradiation. In vitro cell experiments, the nanozyme has remarkable targeting effect, oxygen production capacity, and microwave dynamic effect, which effectively solves the defects of MDT. In the constructed patient-derived xenograft (PDX) model, the nanozyme achieves excellent MDT effect, despite the heterogeneity and complexity of the tumor model that is similar to the histological and pathological features of the patient. The tumor volume in the LZH + MW group is only about 1/20 of that in the control group, and the tumor inhibition rate is as high as 95%. CONCLUSION: The synthesized nanozyme effectively solves the defects of MDT, improves the targeted delivery of microwave sensitizers while regulating the hypoxic microenvironment of tumors, and achieves excellent MDT effect in the constructed PDX model, providing a new strategy for clinical cancer treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-023-02121-9.
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spelling pubmed-106172322023-11-01 Engineering liquid metal-based nanozyme for enhancing microwave dynamic therapy in breast cancer PDX model Wu, Qiong Yu, Yongnian Yu, Xiaorui Du, Qijun Gou, Li Tan, Longfei Fu, Changhui Ren, Xiangling Ren, Jun Xiao, Kai Meng, Xianwei J Nanobiotechnology Research BACKGROUNDS: The novel concept of microwave dynamic therapy (MDT) solves the problem of incomplete tumor eradication caused by non-selective heating and uneven temperature distribution of microwave thermal therapy (MWTT) in clinic, but the poor delivery of microwave sensitizer and the obstacle of tumor hypoxic microenvironment limit the effectiveness of MDT. RESULTS: Herein, we engineer a liquid metal-based nanozyme LM@ZIF@HA (LZH) with eutectic Gallium Indium (EGaIn) as the core, which is coated with CoNi-bimetallic zeolite imidazole framework (ZIF) and hyaluronic acid (HA). The flexibility of the liquid metal and the targeting of HA enable the nanozyme to be effectively endocytosed by tumor cells, solving the problem of poor delivery of microwave sensitizers. Due to the catalase-like activity, the nanozyme catalyze excess H(2)O(2) in the tumor microenvironment to generate O(2), alleviating the restriction of the tumor hypoxic microenvironment and promoting the production of ROS under microwave irradiation. In vitro cell experiments, the nanozyme has remarkable targeting effect, oxygen production capacity, and microwave dynamic effect, which effectively solves the defects of MDT. In the constructed patient-derived xenograft (PDX) model, the nanozyme achieves excellent MDT effect, despite the heterogeneity and complexity of the tumor model that is similar to the histological and pathological features of the patient. The tumor volume in the LZH + MW group is only about 1/20 of that in the control group, and the tumor inhibition rate is as high as 95%. CONCLUSION: The synthesized nanozyme effectively solves the defects of MDT, improves the targeted delivery of microwave sensitizers while regulating the hypoxic microenvironment of tumors, and achieves excellent MDT effect in the constructed PDX model, providing a new strategy for clinical cancer treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-023-02121-9. BioMed Central 2023-10-31 /pmc/articles/PMC10617232/ /pubmed/37904235 http://dx.doi.org/10.1186/s12951-023-02121-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Wu, Qiong
Yu, Yongnian
Yu, Xiaorui
Du, Qijun
Gou, Li
Tan, Longfei
Fu, Changhui
Ren, Xiangling
Ren, Jun
Xiao, Kai
Meng, Xianwei
Engineering liquid metal-based nanozyme for enhancing microwave dynamic therapy in breast cancer PDX model
title Engineering liquid metal-based nanozyme for enhancing microwave dynamic therapy in breast cancer PDX model
title_full Engineering liquid metal-based nanozyme for enhancing microwave dynamic therapy in breast cancer PDX model
title_fullStr Engineering liquid metal-based nanozyme for enhancing microwave dynamic therapy in breast cancer PDX model
title_full_unstemmed Engineering liquid metal-based nanozyme for enhancing microwave dynamic therapy in breast cancer PDX model
title_short Engineering liquid metal-based nanozyme for enhancing microwave dynamic therapy in breast cancer PDX model
title_sort engineering liquid metal-based nanozyme for enhancing microwave dynamic therapy in breast cancer pdx model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617232/
https://www.ncbi.nlm.nih.gov/pubmed/37904235
http://dx.doi.org/10.1186/s12951-023-02121-9
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