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Antitumor Effects of Intra-Arterial Delivery of Albumin-Doxorubicin Nanoparticle Conjugated Microbubbles Combined with Ultrasound-Targeted Microbubble Activation on VX2 Rabbit Liver Tumors

Image-guided intra-arterial therapies play a key role in the management of hepatic malignancies. However, limited clinical outcomes suggest the need for new multifunctional drug delivery systems to enhance local drug concentration while reducing systemic adverse reactions. Therefore, we developed th...

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Autores principales: Lee, Jae Hwan, Moon, Hyungwon, Han, Hyounkoo, Lee, In Joon, Kim, Doyeon, Lee, Hak Jong, Ha, Shin-Woo, Kim, Hyuncheol, Chung, Jin Wook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521081/
https://www.ncbi.nlm.nih.gov/pubmed/31022951
http://dx.doi.org/10.3390/cancers11040581
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author Lee, Jae Hwan
Moon, Hyungwon
Han, Hyounkoo
Lee, In Joon
Kim, Doyeon
Lee, Hak Jong
Ha, Shin-Woo
Kim, Hyuncheol
Chung, Jin Wook
author_facet Lee, Jae Hwan
Moon, Hyungwon
Han, Hyounkoo
Lee, In Joon
Kim, Doyeon
Lee, Hak Jong
Ha, Shin-Woo
Kim, Hyuncheol
Chung, Jin Wook
author_sort Lee, Jae Hwan
collection PubMed
description Image-guided intra-arterial therapies play a key role in the management of hepatic malignancies. However, limited clinical outcomes suggest the need for new multifunctional drug delivery systems to enhance local drug concentration while reducing systemic adverse reactions. Therefore, we developed the albumin-doxorubicin nanoparticle conjugated microbubble (ADMB) to enhance therapeutic efficiency by sonoporation under exposure to ultrasound. ADMB demonstrated a size distribution of 2.33 ± 1.34 µm and a doxorubicin loading efficiency of 82.7%. The echogenicity of ADMBs was sufficiently generated in the 2–9 MHz frequency range and cavitation depended on the strength of the irradiating ultrasound. In the VX2 rabbit tumor model, ADMB enhanced the therapeutic efficiency under ultrasound exposure, compared to free doxorubicin. The intra-arterial administration of ADMBs sufficiently reduced tumor growth by five times, compared to the control group. Changes in the ADC values and viable tumor fraction supported the fact that the antitumor effect of ADMBs were enhanced by evidence of necrosis ratio (over 70%) and survival tumor cell fraction (20%). Liver toxicity was comparable to that of conventional therapies. In conclusion, this study shows that tumor suppression can be sufficiently maximized by combining ultrasound exposure with intra-arterial ADMB administration.
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spelling pubmed-65210812019-05-31 Antitumor Effects of Intra-Arterial Delivery of Albumin-Doxorubicin Nanoparticle Conjugated Microbubbles Combined with Ultrasound-Targeted Microbubble Activation on VX2 Rabbit Liver Tumors Lee, Jae Hwan Moon, Hyungwon Han, Hyounkoo Lee, In Joon Kim, Doyeon Lee, Hak Jong Ha, Shin-Woo Kim, Hyuncheol Chung, Jin Wook Cancers (Basel) Article Image-guided intra-arterial therapies play a key role in the management of hepatic malignancies. However, limited clinical outcomes suggest the need for new multifunctional drug delivery systems to enhance local drug concentration while reducing systemic adverse reactions. Therefore, we developed the albumin-doxorubicin nanoparticle conjugated microbubble (ADMB) to enhance therapeutic efficiency by sonoporation under exposure to ultrasound. ADMB demonstrated a size distribution of 2.33 ± 1.34 µm and a doxorubicin loading efficiency of 82.7%. The echogenicity of ADMBs was sufficiently generated in the 2–9 MHz frequency range and cavitation depended on the strength of the irradiating ultrasound. In the VX2 rabbit tumor model, ADMB enhanced the therapeutic efficiency under ultrasound exposure, compared to free doxorubicin. The intra-arterial administration of ADMBs sufficiently reduced tumor growth by five times, compared to the control group. Changes in the ADC values and viable tumor fraction supported the fact that the antitumor effect of ADMBs were enhanced by evidence of necrosis ratio (over 70%) and survival tumor cell fraction (20%). Liver toxicity was comparable to that of conventional therapies. In conclusion, this study shows that tumor suppression can be sufficiently maximized by combining ultrasound exposure with intra-arterial ADMB administration. MDPI 2019-04-24 /pmc/articles/PMC6521081/ /pubmed/31022951 http://dx.doi.org/10.3390/cancers11040581 Text en © 2019 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
Lee, Jae Hwan
Moon, Hyungwon
Han, Hyounkoo
Lee, In Joon
Kim, Doyeon
Lee, Hak Jong
Ha, Shin-Woo
Kim, Hyuncheol
Chung, Jin Wook
Antitumor Effects of Intra-Arterial Delivery of Albumin-Doxorubicin Nanoparticle Conjugated Microbubbles Combined with Ultrasound-Targeted Microbubble Activation on VX2 Rabbit Liver Tumors
title Antitumor Effects of Intra-Arterial Delivery of Albumin-Doxorubicin Nanoparticle Conjugated Microbubbles Combined with Ultrasound-Targeted Microbubble Activation on VX2 Rabbit Liver Tumors
title_full Antitumor Effects of Intra-Arterial Delivery of Albumin-Doxorubicin Nanoparticle Conjugated Microbubbles Combined with Ultrasound-Targeted Microbubble Activation on VX2 Rabbit Liver Tumors
title_fullStr Antitumor Effects of Intra-Arterial Delivery of Albumin-Doxorubicin Nanoparticle Conjugated Microbubbles Combined with Ultrasound-Targeted Microbubble Activation on VX2 Rabbit Liver Tumors
title_full_unstemmed Antitumor Effects of Intra-Arterial Delivery of Albumin-Doxorubicin Nanoparticle Conjugated Microbubbles Combined with Ultrasound-Targeted Microbubble Activation on VX2 Rabbit Liver Tumors
title_short Antitumor Effects of Intra-Arterial Delivery of Albumin-Doxorubicin Nanoparticle Conjugated Microbubbles Combined with Ultrasound-Targeted Microbubble Activation on VX2 Rabbit Liver Tumors
title_sort antitumor effects of intra-arterial delivery of albumin-doxorubicin nanoparticle conjugated microbubbles combined with ultrasound-targeted microbubble activation on vx2 rabbit liver tumors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521081/
https://www.ncbi.nlm.nih.gov/pubmed/31022951
http://dx.doi.org/10.3390/cancers11040581
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