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Effect of multiple cyclic RGD peptides on tumor accumulation and intratumoral distribution of IRDye 700DX-conjugated polymers
Strategic delivery of IRDye 700DX (photosensitizer) is a key for improving its effect in photodynamic therapy. In this study, we have synthesized IRDye 700DX-conjugated polymers containing multiple cyclic RGD peptides to deliver IRDye 700DX selectively to tumor cells and tumor-associated blood vesse...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970177/ https://www.ncbi.nlm.nih.gov/pubmed/29802410 http://dx.doi.org/10.1038/s41598-018-26593-0 |
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author | Dou, Xuebo Nomoto, Takahiro Takemoto, Hiroyasu Matsui, Makoto Tomoda, Keishiro Nishiyama, Nobuhiro |
author_facet | Dou, Xuebo Nomoto, Takahiro Takemoto, Hiroyasu Matsui, Makoto Tomoda, Keishiro Nishiyama, Nobuhiro |
author_sort | Dou, Xuebo |
collection | PubMed |
description | Strategic delivery of IRDye 700DX (photosensitizer) is a key for improving its effect in photodynamic therapy. In this study, we have synthesized IRDye 700DX-conjugated polymers containing multiple cyclic RGD peptides to deliver IRDye 700DX selectively to tumor cells and tumor-associated blood vessels overexpressing α(v)β(3) integrin. Our polymer has a backbone of hydrophilic poly(ethylene glycol)-poly(L-glutamic acid) block copolymer, and cyclic RGD peptides are conjugated to side chains of the poly(L-glutamic acid) while IRDye 700DX is conjugated to the terminal of poly(ethylene glycol). The polymers exhibited selective accumulation to the target sites in a subcutaneous solid tumor, and the accumulation was augmented with the increased number of cyclic RGD peptides. More importantly, the polymer containing 15 cyclic RGD peptides in one construct revealed preferential accumulation on the tumor-associated blood vessels without compromising penetration to deep portions of the tumor, thereby drastically inhibiting tumor growth upon photoirradiation, while the polymer containing 5 cyclic RGD peptides showed moderate antitumor activity despite efficient accumulation in the tumor with almost homogenous intratumoral distribution. These results suggest that controlling the intratumoral distribution of IRDye 700DX is critical for successful PDT, and our polymer containing multiple cyclic RGD peptides may be a promising carrier for this spatial control. |
format | Online Article Text |
id | pubmed-5970177 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-59701772018-05-30 Effect of multiple cyclic RGD peptides on tumor accumulation and intratumoral distribution of IRDye 700DX-conjugated polymers Dou, Xuebo Nomoto, Takahiro Takemoto, Hiroyasu Matsui, Makoto Tomoda, Keishiro Nishiyama, Nobuhiro Sci Rep Article Strategic delivery of IRDye 700DX (photosensitizer) is a key for improving its effect in photodynamic therapy. In this study, we have synthesized IRDye 700DX-conjugated polymers containing multiple cyclic RGD peptides to deliver IRDye 700DX selectively to tumor cells and tumor-associated blood vessels overexpressing α(v)β(3) integrin. Our polymer has a backbone of hydrophilic poly(ethylene glycol)-poly(L-glutamic acid) block copolymer, and cyclic RGD peptides are conjugated to side chains of the poly(L-glutamic acid) while IRDye 700DX is conjugated to the terminal of poly(ethylene glycol). The polymers exhibited selective accumulation to the target sites in a subcutaneous solid tumor, and the accumulation was augmented with the increased number of cyclic RGD peptides. More importantly, the polymer containing 15 cyclic RGD peptides in one construct revealed preferential accumulation on the tumor-associated blood vessels without compromising penetration to deep portions of the tumor, thereby drastically inhibiting tumor growth upon photoirradiation, while the polymer containing 5 cyclic RGD peptides showed moderate antitumor activity despite efficient accumulation in the tumor with almost homogenous intratumoral distribution. These results suggest that controlling the intratumoral distribution of IRDye 700DX is critical for successful PDT, and our polymer containing multiple cyclic RGD peptides may be a promising carrier for this spatial control. Nature Publishing Group UK 2018-05-25 /pmc/articles/PMC5970177/ /pubmed/29802410 http://dx.doi.org/10.1038/s41598-018-26593-0 Text en © The Author(s) 2018 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Dou, Xuebo Nomoto, Takahiro Takemoto, Hiroyasu Matsui, Makoto Tomoda, Keishiro Nishiyama, Nobuhiro Effect of multiple cyclic RGD peptides on tumor accumulation and intratumoral distribution of IRDye 700DX-conjugated polymers |
title | Effect of multiple cyclic RGD peptides on tumor accumulation and intratumoral distribution of IRDye 700DX-conjugated polymers |
title_full | Effect of multiple cyclic RGD peptides on tumor accumulation and intratumoral distribution of IRDye 700DX-conjugated polymers |
title_fullStr | Effect of multiple cyclic RGD peptides on tumor accumulation and intratumoral distribution of IRDye 700DX-conjugated polymers |
title_full_unstemmed | Effect of multiple cyclic RGD peptides on tumor accumulation and intratumoral distribution of IRDye 700DX-conjugated polymers |
title_short | Effect of multiple cyclic RGD peptides on tumor accumulation and intratumoral distribution of IRDye 700DX-conjugated polymers |
title_sort | effect of multiple cyclic rgd peptides on tumor accumulation and intratumoral distribution of irdye 700dx-conjugated polymers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970177/ https://www.ncbi.nlm.nih.gov/pubmed/29802410 http://dx.doi.org/10.1038/s41598-018-26593-0 |
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