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Single enzyme loaded nanoparticles for combinational ultrasound-guided focused ultrasound ablation and hypoxia-relieved chemotherapy

Constructing nanosystems that synergistically combine therapeutic and diagnostic features is of great interest to the nanomedicine community but also remains a tremendous challenge. Methods: In this work, we report novel catalytic nanoparticles composed of the enzyme catalase, encapsulated in a poly...

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Autores principales: Zhu, Jianzhi, Li, Zhicong, Zhang, Changchang, Lin, Lizhou, Cao, Shoupeng, Che, Hailong, Shi, Xiangyang, Wang, Han, van Hest, Jan C. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857069/
https://www.ncbi.nlm.nih.gov/pubmed/31754380
http://dx.doi.org/10.7150/thno.37054
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author Zhu, Jianzhi
Li, Zhicong
Zhang, Changchang
Lin, Lizhou
Cao, Shoupeng
Che, Hailong
Shi, Xiangyang
Wang, Han
van Hest, Jan C. M.
author_facet Zhu, Jianzhi
Li, Zhicong
Zhang, Changchang
Lin, Lizhou
Cao, Shoupeng
Che, Hailong
Shi, Xiangyang
Wang, Han
van Hest, Jan C. M.
author_sort Zhu, Jianzhi
collection PubMed
description Constructing nanosystems that synergistically combine therapeutic and diagnostic features is of great interest to the nanomedicine community but also remains a tremendous challenge. Methods: In this work, we report novel catalytic nanoparticles composed of the enzyme catalase, encapsulated in a polymer shell and surface decorated with pH-sensitive poly(ethylene glycol) (PEGylated nCAT). These nanoparticles were used as a promoter for ultrasound (US)-guided focused ultrasound (FUS) ablation and hypoxia alleviation for application in Doxorubicin-based chemotherapy. Results: The PEGylated nCAT produced highly effectively O(2) from endogenous H(2)O(2) to ameliorate the hypoxic and therefore poor-acoustic tumor environment. The generated O(2) was utilized as 1) a contrast agent for US imaging; 2) strengthening agent for FUS ablation and 3) normoxia inducer to enhance chemotherapeutic efficacy. The PEGylated nCAT exhibited favorable enzyme activity after long-term storage, and after exposure to proteolytic conditions and elevated temperatures. The pH-responsive PEGylation contributed on the one hand to an extended in vivo circulation time over 48 h and on the other hand enabled PEG cleavage in the vicinity of cancer cells to facilitate cellular uptake. Conclusion: The developed PEGylated nCAT can therefore effectively combine US-guided FUS and chemotherapy and can be regarded as a highly promising theranostic platform.
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spelling pubmed-68570692019-11-21 Single enzyme loaded nanoparticles for combinational ultrasound-guided focused ultrasound ablation and hypoxia-relieved chemotherapy Zhu, Jianzhi Li, Zhicong Zhang, Changchang Lin, Lizhou Cao, Shoupeng Che, Hailong Shi, Xiangyang Wang, Han van Hest, Jan C. M. Theranostics Research Paper Constructing nanosystems that synergistically combine therapeutic and diagnostic features is of great interest to the nanomedicine community but also remains a tremendous challenge. Methods: In this work, we report novel catalytic nanoparticles composed of the enzyme catalase, encapsulated in a polymer shell and surface decorated with pH-sensitive poly(ethylene glycol) (PEGylated nCAT). These nanoparticles were used as a promoter for ultrasound (US)-guided focused ultrasound (FUS) ablation and hypoxia alleviation for application in Doxorubicin-based chemotherapy. Results: The PEGylated nCAT produced highly effectively O(2) from endogenous H(2)O(2) to ameliorate the hypoxic and therefore poor-acoustic tumor environment. The generated O(2) was utilized as 1) a contrast agent for US imaging; 2) strengthening agent for FUS ablation and 3) normoxia inducer to enhance chemotherapeutic efficacy. The PEGylated nCAT exhibited favorable enzyme activity after long-term storage, and after exposure to proteolytic conditions and elevated temperatures. The pH-responsive PEGylation contributed on the one hand to an extended in vivo circulation time over 48 h and on the other hand enabled PEG cleavage in the vicinity of cancer cells to facilitate cellular uptake. Conclusion: The developed PEGylated nCAT can therefore effectively combine US-guided FUS and chemotherapy and can be regarded as a highly promising theranostic platform. Ivyspring International Publisher 2019-10-17 /pmc/articles/PMC6857069/ /pubmed/31754380 http://dx.doi.org/10.7150/thno.37054 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Zhu, Jianzhi
Li, Zhicong
Zhang, Changchang
Lin, Lizhou
Cao, Shoupeng
Che, Hailong
Shi, Xiangyang
Wang, Han
van Hest, Jan C. M.
Single enzyme loaded nanoparticles for combinational ultrasound-guided focused ultrasound ablation and hypoxia-relieved chemotherapy
title Single enzyme loaded nanoparticles for combinational ultrasound-guided focused ultrasound ablation and hypoxia-relieved chemotherapy
title_full Single enzyme loaded nanoparticles for combinational ultrasound-guided focused ultrasound ablation and hypoxia-relieved chemotherapy
title_fullStr Single enzyme loaded nanoparticles for combinational ultrasound-guided focused ultrasound ablation and hypoxia-relieved chemotherapy
title_full_unstemmed Single enzyme loaded nanoparticles for combinational ultrasound-guided focused ultrasound ablation and hypoxia-relieved chemotherapy
title_short Single enzyme loaded nanoparticles for combinational ultrasound-guided focused ultrasound ablation and hypoxia-relieved chemotherapy
title_sort single enzyme loaded nanoparticles for combinational ultrasound-guided focused ultrasound ablation and hypoxia-relieved chemotherapy
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857069/
https://www.ncbi.nlm.nih.gov/pubmed/31754380
http://dx.doi.org/10.7150/thno.37054
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