Cargando…
Deep Tumor Penetration of Doxorubicin-Loaded Glycol Chitosan Nanoparticles Using High-Intensity Focused Ultrasound
The dense extracellular matrix (ECM) in heterogeneous tumor tissues can prevent the deep tumor penetration of drug-loaded nanoparticles, resulting in a limited therapeutic efficacy in cancer treatment. Herein, we suggest that the deep tumor penetration of doxorubicin (DOX)-loaded glycol chitosan nan...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650702/ https://www.ncbi.nlm.nih.gov/pubmed/33076520 http://dx.doi.org/10.3390/pharmaceutics12100974 |
_version_ | 1783607537837277184 |
---|---|
author | Choi, Yongwhan Han, Hyounkoo Jeon, Sangmin Yoon, Hong Yeol Kim, Hyuncheol Kwon, Ick Chan Kim, Kwangmeyung |
author_facet | Choi, Yongwhan Han, Hyounkoo Jeon, Sangmin Yoon, Hong Yeol Kim, Hyuncheol Kwon, Ick Chan Kim, Kwangmeyung |
author_sort | Choi, Yongwhan |
collection | PubMed |
description | The dense extracellular matrix (ECM) in heterogeneous tumor tissues can prevent the deep tumor penetration of drug-loaded nanoparticles, resulting in a limited therapeutic efficacy in cancer treatment. Herein, we suggest that the deep tumor penetration of doxorubicin (DOX)-loaded glycol chitosan nanoparticles (CNPs) can be improved using high-intensity focused ultrasound (HIFU) technology. Firstly, we prepared amphiphilic glycol chitosan-5β-cholanic acid conjugates that can self-assemble to form stable nanoparticles with an average of 283.7 ± 5.3 nm. Next, the anticancer drug DOX was simply loaded into the CNPs via a dialysis method. DOX-loaded CNPs (DOX-CNPs) had stable nanoparticle structures with an average size of 265.9 ± 35.5 nm in aqueous condition. In cultured cells, HIFU-treated DOX-CNPs showed rapid drug release and enhanced cellular uptake in A549 cells, resulting in increased cytotoxicity, compared to untreated DOX-CNPs. In ECM-rich A549 tumor-bearing mice, the tumor-targeting efficacy of intravenously injected DOX-CNPs with HIFU treatment was 1.84 times higher than that of untreated DOX-CNPs. Furthermore, the deep tumor penetration of HIFU-treated DOX-CNPs was clearly observed at targeted tumor tissues, due to the destruction of the ECM structure via HIFU treatment. Finally, HIFU-treated DOX-CNPs greatly increased the therapeutic efficacy at ECM-rich A549 tumor-bearing mice, compared to free DOX and untreated DOX-CNPs. This deep penetration of drug-loaded nanoparticles via HIFU treatment is a promising strategy to treat heterogeneous tumors with dense ECM structures. |
format | Online Article Text |
id | pubmed-7650702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76507022020-11-10 Deep Tumor Penetration of Doxorubicin-Loaded Glycol Chitosan Nanoparticles Using High-Intensity Focused Ultrasound Choi, Yongwhan Han, Hyounkoo Jeon, Sangmin Yoon, Hong Yeol Kim, Hyuncheol Kwon, Ick Chan Kim, Kwangmeyung Pharmaceutics Article The dense extracellular matrix (ECM) in heterogeneous tumor tissues can prevent the deep tumor penetration of drug-loaded nanoparticles, resulting in a limited therapeutic efficacy in cancer treatment. Herein, we suggest that the deep tumor penetration of doxorubicin (DOX)-loaded glycol chitosan nanoparticles (CNPs) can be improved using high-intensity focused ultrasound (HIFU) technology. Firstly, we prepared amphiphilic glycol chitosan-5β-cholanic acid conjugates that can self-assemble to form stable nanoparticles with an average of 283.7 ± 5.3 nm. Next, the anticancer drug DOX was simply loaded into the CNPs via a dialysis method. DOX-loaded CNPs (DOX-CNPs) had stable nanoparticle structures with an average size of 265.9 ± 35.5 nm in aqueous condition. In cultured cells, HIFU-treated DOX-CNPs showed rapid drug release and enhanced cellular uptake in A549 cells, resulting in increased cytotoxicity, compared to untreated DOX-CNPs. In ECM-rich A549 tumor-bearing mice, the tumor-targeting efficacy of intravenously injected DOX-CNPs with HIFU treatment was 1.84 times higher than that of untreated DOX-CNPs. Furthermore, the deep tumor penetration of HIFU-treated DOX-CNPs was clearly observed at targeted tumor tissues, due to the destruction of the ECM structure via HIFU treatment. Finally, HIFU-treated DOX-CNPs greatly increased the therapeutic efficacy at ECM-rich A549 tumor-bearing mice, compared to free DOX and untreated DOX-CNPs. This deep penetration of drug-loaded nanoparticles via HIFU treatment is a promising strategy to treat heterogeneous tumors with dense ECM structures. MDPI 2020-10-15 /pmc/articles/PMC7650702/ /pubmed/33076520 http://dx.doi.org/10.3390/pharmaceutics12100974 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Choi, Yongwhan Han, Hyounkoo Jeon, Sangmin Yoon, Hong Yeol Kim, Hyuncheol Kwon, Ick Chan Kim, Kwangmeyung Deep Tumor Penetration of Doxorubicin-Loaded Glycol Chitosan Nanoparticles Using High-Intensity Focused Ultrasound |
title | Deep Tumor Penetration of Doxorubicin-Loaded Glycol Chitosan Nanoparticles Using High-Intensity Focused Ultrasound |
title_full | Deep Tumor Penetration of Doxorubicin-Loaded Glycol Chitosan Nanoparticles Using High-Intensity Focused Ultrasound |
title_fullStr | Deep Tumor Penetration of Doxorubicin-Loaded Glycol Chitosan Nanoparticles Using High-Intensity Focused Ultrasound |
title_full_unstemmed | Deep Tumor Penetration of Doxorubicin-Loaded Glycol Chitosan Nanoparticles Using High-Intensity Focused Ultrasound |
title_short | Deep Tumor Penetration of Doxorubicin-Loaded Glycol Chitosan Nanoparticles Using High-Intensity Focused Ultrasound |
title_sort | deep tumor penetration of doxorubicin-loaded glycol chitosan nanoparticles using high-intensity focused ultrasound |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650702/ https://www.ncbi.nlm.nih.gov/pubmed/33076520 http://dx.doi.org/10.3390/pharmaceutics12100974 |
work_keys_str_mv | AT choiyongwhan deeptumorpenetrationofdoxorubicinloadedglycolchitosannanoparticlesusinghighintensityfocusedultrasound AT hanhyounkoo deeptumorpenetrationofdoxorubicinloadedglycolchitosannanoparticlesusinghighintensityfocusedultrasound AT jeonsangmin deeptumorpenetrationofdoxorubicinloadedglycolchitosannanoparticlesusinghighintensityfocusedultrasound AT yoonhongyeol deeptumorpenetrationofdoxorubicinloadedglycolchitosannanoparticlesusinghighintensityfocusedultrasound AT kimhyuncheol deeptumorpenetrationofdoxorubicinloadedglycolchitosannanoparticlesusinghighintensityfocusedultrasound AT kwonickchan deeptumorpenetrationofdoxorubicinloadedglycolchitosannanoparticlesusinghighintensityfocusedultrasound AT kimkwangmeyung deeptumorpenetrationofdoxorubicinloadedglycolchitosannanoparticlesusinghighintensityfocusedultrasound |