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Tumor Microenvironment-Responsive Polymeric iRGD and Doxorubicin Conjugates Reduce Spontaneous Lung Metastasis in an Orthotopic Breast Cancer Model

Tremendous progress has been made in the field of nanomedicine for cancer treatment. However, most of the research to date has been focused on inhibiting primary tumor growth with comparatively less efforts directed towards managing tumor metastasis. Here, we introduce a polymeric conjugate P-DOX-iR...

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Autores principales: Peng, Zheng-Hong, Jogdeo, Chinmay M., Li, Jing, Xie, Ying, Wang, Yazhe, Sheinin, Yuri M., Kopeček, Jindřich, Oupický, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9416753/
https://www.ncbi.nlm.nih.gov/pubmed/36015351
http://dx.doi.org/10.3390/pharmaceutics14081725
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author Peng, Zheng-Hong
Jogdeo, Chinmay M.
Li, Jing
Xie, Ying
Wang, Yazhe
Sheinin, Yuri M.
Kopeček, Jindřich
Oupický, David
author_facet Peng, Zheng-Hong
Jogdeo, Chinmay M.
Li, Jing
Xie, Ying
Wang, Yazhe
Sheinin, Yuri M.
Kopeček, Jindřich
Oupický, David
author_sort Peng, Zheng-Hong
collection PubMed
description Tremendous progress has been made in the field of nanomedicine for cancer treatment. However, most of the research to date has been focused on inhibiting primary tumor growth with comparatively less efforts directed towards managing tumor metastasis. Here, we introduce a polymeric conjugate P-DOX-iRGD that not only significantly suppressed primary tumor growth but also substantially inhibited pulmonary metastasis in an orthotopic mouse model of breast cancer. In addition, treatment with P-DOX-iRGD markedly reduced breast cancer-induced splenomegaly and liver hematopoiesis. Interestingly, contrasting results were seen for the free form and polymeric form of DOX in vitro and in vivo, which may be attributed to the enhanced permeability and retention (EPR) effect.
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spelling pubmed-94167532022-08-27 Tumor Microenvironment-Responsive Polymeric iRGD and Doxorubicin Conjugates Reduce Spontaneous Lung Metastasis in an Orthotopic Breast Cancer Model Peng, Zheng-Hong Jogdeo, Chinmay M. Li, Jing Xie, Ying Wang, Yazhe Sheinin, Yuri M. Kopeček, Jindřich Oupický, David Pharmaceutics Article Tremendous progress has been made in the field of nanomedicine for cancer treatment. However, most of the research to date has been focused on inhibiting primary tumor growth with comparatively less efforts directed towards managing tumor metastasis. Here, we introduce a polymeric conjugate P-DOX-iRGD that not only significantly suppressed primary tumor growth but also substantially inhibited pulmonary metastasis in an orthotopic mouse model of breast cancer. In addition, treatment with P-DOX-iRGD markedly reduced breast cancer-induced splenomegaly and liver hematopoiesis. Interestingly, contrasting results were seen for the free form and polymeric form of DOX in vitro and in vivo, which may be attributed to the enhanced permeability and retention (EPR) effect. MDPI 2022-08-18 /pmc/articles/PMC9416753/ /pubmed/36015351 http://dx.doi.org/10.3390/pharmaceutics14081725 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Peng, Zheng-Hong
Jogdeo, Chinmay M.
Li, Jing
Xie, Ying
Wang, Yazhe
Sheinin, Yuri M.
Kopeček, Jindřich
Oupický, David
Tumor Microenvironment-Responsive Polymeric iRGD and Doxorubicin Conjugates Reduce Spontaneous Lung Metastasis in an Orthotopic Breast Cancer Model
title Tumor Microenvironment-Responsive Polymeric iRGD and Doxorubicin Conjugates Reduce Spontaneous Lung Metastasis in an Orthotopic Breast Cancer Model
title_full Tumor Microenvironment-Responsive Polymeric iRGD and Doxorubicin Conjugates Reduce Spontaneous Lung Metastasis in an Orthotopic Breast Cancer Model
title_fullStr Tumor Microenvironment-Responsive Polymeric iRGD and Doxorubicin Conjugates Reduce Spontaneous Lung Metastasis in an Orthotopic Breast Cancer Model
title_full_unstemmed Tumor Microenvironment-Responsive Polymeric iRGD and Doxorubicin Conjugates Reduce Spontaneous Lung Metastasis in an Orthotopic Breast Cancer Model
title_short Tumor Microenvironment-Responsive Polymeric iRGD and Doxorubicin Conjugates Reduce Spontaneous Lung Metastasis in an Orthotopic Breast Cancer Model
title_sort tumor microenvironment-responsive polymeric irgd and doxorubicin conjugates reduce spontaneous lung metastasis in an orthotopic breast cancer model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9416753/
https://www.ncbi.nlm.nih.gov/pubmed/36015351
http://dx.doi.org/10.3390/pharmaceutics14081725
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