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Silk fibroin-based embolic agent for transhepatic artery embolization with multiple therapeutic potentials

BACKGROUND: The excellent physicochemical and biomedical properties make silk fibroin (SF) suitable for the development of biomedical materials. In this research, the silk fibroin microspheres (SFMS) were customized in two size ranges, and then carried gold nanoparticles or doxorubicin to evaluate t...

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Autores principales: Shi, Linlin, Li, Danni, Tong, Qianqian, Jia, Guorong, Li, Xiaohong, Zhang, Lan, Han, Qingqing, Li, Rou, Zuo, Changjing, Zhang, Wei, Li, Xiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439629/
https://www.ncbi.nlm.nih.gov/pubmed/37598140
http://dx.doi.org/10.1186/s12951-023-02032-9
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author Shi, Linlin
Li, Danni
Tong, Qianqian
Jia, Guorong
Li, Xiaohong
Zhang, Lan
Han, Qingqing
Li, Rou
Zuo, Changjing
Zhang, Wei
Li, Xiao
author_facet Shi, Linlin
Li, Danni
Tong, Qianqian
Jia, Guorong
Li, Xiaohong
Zhang, Lan
Han, Qingqing
Li, Rou
Zuo, Changjing
Zhang, Wei
Li, Xiao
author_sort Shi, Linlin
collection PubMed
description BACKGROUND: The excellent physicochemical and biomedical properties make silk fibroin (SF) suitable for the development of biomedical materials. In this research, the silk fibroin microspheres (SFMS) were customized in two size ranges, and then carried gold nanoparticles or doxorubicin to evaluate the performance of drug loading and releasing. Embolization efficiency was evaluated in rat caudal artery and rabbit auricular artery, and the in vivo distribution of iodinated SFMS ((125)I/(131)I-SFMS) after embolization of rat hepatic artery was dynamically recorded by SPECT. Transhepatic arterial radioembolization (TARE) with (131)I-SFMS was performed on rat models with liver cancer. The whole procedure of selective internal radiation was recorded with SPECT/CT, and the therapeutic effects were evaluated with (18) F-FDG PET/CT. Lastly, the enzymatic degradation was recorded and followed with the evaluation of particle size on clearance of sub-micron silk fibroin. RESULTS: SFMS were of smooth surface and regular shape with pervasive pores on the surface and inside the microspheres, and of suitable size range for TAE. Drug-loading functionalized SFMS with chemotherapy or radio-sensitization, and the enhanced therapeutic effects were proved in treating HUH-7 cells as lasting doxorubicin release or more lethal radiation. For artery embolization, SFMS effectively blocked the blood supply; when (131)I-SFMS serving as the embolic agent, the good labeling stability and embolization performance guaranteed the favorable therapeutic effects in treating in situ liver tumor. At the 5th day post TARE with 37 MBq/3 mg (131)I-SFMS per mice, tumor activity was quickly inhibited to a comparable glucose metabolism level with surrounding normal liver. More importantly, for the fragments of biodegradable SFMS, smaller sized SF (< 800 nm) metabolized in gastrointestinal tract and excreted by the urinary system, while SF (> 800 nm) entered the liver within 72 h for further metabolism. CONCLUSION: The feasibility of SFMS as degradable TARE agent for liver cancer was primarily proved as providing multiple therapeutic potentials. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-023-02032-9.
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spelling pubmed-104396292023-08-20 Silk fibroin-based embolic agent for transhepatic artery embolization with multiple therapeutic potentials Shi, Linlin Li, Danni Tong, Qianqian Jia, Guorong Li, Xiaohong Zhang, Lan Han, Qingqing Li, Rou Zuo, Changjing Zhang, Wei Li, Xiao J Nanobiotechnology Research BACKGROUND: The excellent physicochemical and biomedical properties make silk fibroin (SF) suitable for the development of biomedical materials. In this research, the silk fibroin microspheres (SFMS) were customized in two size ranges, and then carried gold nanoparticles or doxorubicin to evaluate the performance of drug loading and releasing. Embolization efficiency was evaluated in rat caudal artery and rabbit auricular artery, and the in vivo distribution of iodinated SFMS ((125)I/(131)I-SFMS) after embolization of rat hepatic artery was dynamically recorded by SPECT. Transhepatic arterial radioembolization (TARE) with (131)I-SFMS was performed on rat models with liver cancer. The whole procedure of selective internal radiation was recorded with SPECT/CT, and the therapeutic effects were evaluated with (18) F-FDG PET/CT. Lastly, the enzymatic degradation was recorded and followed with the evaluation of particle size on clearance of sub-micron silk fibroin. RESULTS: SFMS were of smooth surface and regular shape with pervasive pores on the surface and inside the microspheres, and of suitable size range for TAE. Drug-loading functionalized SFMS with chemotherapy or radio-sensitization, and the enhanced therapeutic effects were proved in treating HUH-7 cells as lasting doxorubicin release or more lethal radiation. For artery embolization, SFMS effectively blocked the blood supply; when (131)I-SFMS serving as the embolic agent, the good labeling stability and embolization performance guaranteed the favorable therapeutic effects in treating in situ liver tumor. At the 5th day post TARE with 37 MBq/3 mg (131)I-SFMS per mice, tumor activity was quickly inhibited to a comparable glucose metabolism level with surrounding normal liver. More importantly, for the fragments of biodegradable SFMS, smaller sized SF (< 800 nm) metabolized in gastrointestinal tract and excreted by the urinary system, while SF (> 800 nm) entered the liver within 72 h for further metabolism. CONCLUSION: The feasibility of SFMS as degradable TARE agent for liver cancer was primarily proved as providing multiple therapeutic potentials. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-023-02032-9. BioMed Central 2023-08-19 /pmc/articles/PMC10439629/ /pubmed/37598140 http://dx.doi.org/10.1186/s12951-023-02032-9 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
Shi, Linlin
Li, Danni
Tong, Qianqian
Jia, Guorong
Li, Xiaohong
Zhang, Lan
Han, Qingqing
Li, Rou
Zuo, Changjing
Zhang, Wei
Li, Xiao
Silk fibroin-based embolic agent for transhepatic artery embolization with multiple therapeutic potentials
title Silk fibroin-based embolic agent for transhepatic artery embolization with multiple therapeutic potentials
title_full Silk fibroin-based embolic agent for transhepatic artery embolization with multiple therapeutic potentials
title_fullStr Silk fibroin-based embolic agent for transhepatic artery embolization with multiple therapeutic potentials
title_full_unstemmed Silk fibroin-based embolic agent for transhepatic artery embolization with multiple therapeutic potentials
title_short Silk fibroin-based embolic agent for transhepatic artery embolization with multiple therapeutic potentials
title_sort silk fibroin-based embolic agent for transhepatic artery embolization with multiple therapeutic potentials
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439629/
https://www.ncbi.nlm.nih.gov/pubmed/37598140
http://dx.doi.org/10.1186/s12951-023-02032-9
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