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111In-labelled polymeric nanoparticles incorporating a ruthenium-based radiosensitizer for EGFR-targeted combination therapy in oesophageal cancer cells

Martin Gill Orcid Logo, Jyothi U. Menon, Paul J. Jarman, Joshua Owen, Irini Skaripa-Koukelli, Sarah Able, Jim A. Thomas, Robert Carlisle, Katherine A. Vallis

Nanoscale, Volume: 10, Issue: 22, Pages: 10596 - 10608

Swansea University Author: Martin Gill Orcid Logo

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DOI (Published version): 10.1039/c7nr09606b

Abstract

Radiolabelled, drug-loaded nanoparticles may combine the theranostic properties of radionuclides, the controlled release of chemotherapy and cancer cell targeting. Here, we report the preparation of poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface conjugated to DTPA-hEGF (DTPA = diethylene...

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Published in: Nanoscale
ISSN: 2040-3364 2040-3372
Published: Royal Society of Chemistry (RSC) 2018
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URI: https://cronfa.swan.ac.uk/Record/cronfa52924
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Here, we report the preparation of poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface conjugated to DTPA-hEGF (DTPA = diethylenetriaminepentaacetic acid, hEGF = human epidermal growth factor) and encapsulating the ruthenium-based DNA replication inhibitor and radiosensitizer Ru(phen)2(tpphz)2+ (phen = 1,10-phenanthroline, tpphz = tetrapyridophenazine) Ru1. The functionalized PLGA surface incorporates the metal ion chelator DTPA for radiolabelling and the targeting ligand for EGF receptor (EGFR). Nanoparticles radiolabelled with 111In are taken up preferentially by EGFR-overexpressing oesophageal cancer cells, where they exhibit radiotoxicity through the generation of cellular DNA damage. Moreover, nanoparticle co-delivery of Ru1 alongside 111In results in decreased cell survival compared to single-agent formulations; an effect that occurs through DNA damage enhancement and an additive relationship between 111In and Ru1. Substantially decreased uptake and radiotoxicity of nanoparticles towards normal human fibroblasts and oesophageal cancer cells with normal EGFR levels is observed. 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spelling 2025-04-30T14:36:37.2308142 v2 52924 2019-12-02 111In-labelled polymeric nanoparticles incorporating a ruthenium-based radiosensitizer for EGFR-targeted combination therapy in oesophageal cancer cells 485d85b532851e8863cd19c6af7e00f7 0000-0002-1371-5676 Martin Gill Martin Gill true false 2019-12-02 EAAS Radiolabelled, drug-loaded nanoparticles may combine the theranostic properties of radionuclides, the controlled release of chemotherapy and cancer cell targeting. Here, we report the preparation of poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface conjugated to DTPA-hEGF (DTPA = diethylenetriaminepentaacetic acid, hEGF = human epidermal growth factor) and encapsulating the ruthenium-based DNA replication inhibitor and radiosensitizer Ru(phen)2(tpphz)2+ (phen = 1,10-phenanthroline, tpphz = tetrapyridophenazine) Ru1. The functionalized PLGA surface incorporates the metal ion chelator DTPA for radiolabelling and the targeting ligand for EGF receptor (EGFR). Nanoparticles radiolabelled with 111In are taken up preferentially by EGFR-overexpressing oesophageal cancer cells, where they exhibit radiotoxicity through the generation of cellular DNA damage. Moreover, nanoparticle co-delivery of Ru1 alongside 111In results in decreased cell survival compared to single-agent formulations; an effect that occurs through DNA damage enhancement and an additive relationship between 111In and Ru1. Substantially decreased uptake and radiotoxicity of nanoparticles towards normal human fibroblasts and oesophageal cancer cells with normal EGFR levels is observed. This work demonstrates nanoparticle co-delivery of a therapeutic radionuclide plus a ruthenium-based radiosensitizer can achieve combinational and targeted therapeutic effects in cancer cells that overexpress EGFR. Journal Article Nanoscale 10 22 10596 10608 Royal Society of Chemistry (RSC) 2040-3364 2040-3372 29 5 2018 2018-05-29 10.1039/c7nr09606b COLLEGE NANME Engineering and Applied Sciences School COLLEGE CODE EAAS Swansea University Another institution paid the OA fee M. R. G. and K. A. V. received financial support from Cancer Research UK (C5255/A15935), the Medical Research Council (MC_PC_12004) and a Medical Research Council Confidence in Concept award. K. A. V., J. O., I. S. K., R. C. and J. U. M. received support from the Engineering and Physical Sciences Research Council (EP/L024012/1). We thank P. Holdship and F. Larner for ICP-MS analysis, and G. Brown and V. Kersemans for assistance. 2025-04-30T14:36:37.2308142 2019-12-02T15:53:23.4763687 Faculty of Science and Engineering School of Engineering and Applied Sciences - Chemistry Martin Gill 0000-0002-1371-5676 1 Jyothi U. Menon 2 Paul J. Jarman 3 Joshua Owen 4 Irini Skaripa-Koukelli 5 Sarah Able 6 Jim A. Thomas 7 Robert Carlisle 8 Katherine A. Vallis 9 52924__16420__9f092f9e5464425d8e4d6fd4efa4a8f5.pdf 52924.pdf 2020-01-24T11:03:29.2726847 Output 2777778 application/pdf Version of Record true Distributed under the terms of a Creative Commons Attribution Licence (CC-BY) 3.0 true eng https://creativecommons.org/licenses/by/3.0/
title 111In-labelled polymeric nanoparticles incorporating a ruthenium-based radiosensitizer for EGFR-targeted combination therapy in oesophageal cancer cells
spellingShingle 111In-labelled polymeric nanoparticles incorporating a ruthenium-based radiosensitizer for EGFR-targeted combination therapy in oesophageal cancer cells
Martin Gill
title_short 111In-labelled polymeric nanoparticles incorporating a ruthenium-based radiosensitizer for EGFR-targeted combination therapy in oesophageal cancer cells
title_full 111In-labelled polymeric nanoparticles incorporating a ruthenium-based radiosensitizer for EGFR-targeted combination therapy in oesophageal cancer cells
title_fullStr 111In-labelled polymeric nanoparticles incorporating a ruthenium-based radiosensitizer for EGFR-targeted combination therapy in oesophageal cancer cells
title_full_unstemmed 111In-labelled polymeric nanoparticles incorporating a ruthenium-based radiosensitizer for EGFR-targeted combination therapy in oesophageal cancer cells
title_sort 111In-labelled polymeric nanoparticles incorporating a ruthenium-based radiosensitizer for EGFR-targeted combination therapy in oesophageal cancer cells
author_id_str_mv 485d85b532851e8863cd19c6af7e00f7
author_id_fullname_str_mv 485d85b532851e8863cd19c6af7e00f7_***_Martin Gill
author Martin Gill
author2 Martin Gill
Jyothi U. Menon
Paul J. Jarman
Joshua Owen
Irini Skaripa-Koukelli
Sarah Able
Jim A. Thomas
Robert Carlisle
Katherine A. Vallis
format Journal article
container_title Nanoscale
container_volume 10
container_issue 22
container_start_page 10596
publishDate 2018
institution Swansea University
issn 2040-3364
2040-3372
doi_str_mv 10.1039/c7nr09606b
publisher Royal Society of Chemistry (RSC)
college_str Faculty of Science and Engineering
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hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Engineering and Applied Sciences - Chemistry{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Chemistry
document_store_str 1
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description Radiolabelled, drug-loaded nanoparticles may combine the theranostic properties of radionuclides, the controlled release of chemotherapy and cancer cell targeting. Here, we report the preparation of poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface conjugated to DTPA-hEGF (DTPA = diethylenetriaminepentaacetic acid, hEGF = human epidermal growth factor) and encapsulating the ruthenium-based DNA replication inhibitor and radiosensitizer Ru(phen)2(tpphz)2+ (phen = 1,10-phenanthroline, tpphz = tetrapyridophenazine) Ru1. The functionalized PLGA surface incorporates the metal ion chelator DTPA for radiolabelling and the targeting ligand for EGF receptor (EGFR). Nanoparticles radiolabelled with 111In are taken up preferentially by EGFR-overexpressing oesophageal cancer cells, where they exhibit radiotoxicity through the generation of cellular DNA damage. Moreover, nanoparticle co-delivery of Ru1 alongside 111In results in decreased cell survival compared to single-agent formulations; an effect that occurs through DNA damage enhancement and an additive relationship between 111In and Ru1. Substantially decreased uptake and radiotoxicity of nanoparticles towards normal human fibroblasts and oesophageal cancer cells with normal EGFR levels is observed. This work demonstrates nanoparticle co-delivery of a therapeutic radionuclide plus a ruthenium-based radiosensitizer can achieve combinational and targeted therapeutic effects in cancer cells that overexpress EGFR.
published_date 2018-05-29T04:40:48Z
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