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Covalent IR820-PEG-diamine nanoconjugates for theranostic applications in cancer
Near-infrared dyes can be used as theranostic agents in cancer management, based on their optical imaging and localized hyperthermia capabilities. However, their clinical translatability is limited by issues such as photobleaching, short circulation times, and nonspecific biodistribution. Nanoconjug...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200025/ https://www.ncbi.nlm.nih.gov/pubmed/25336944 http://dx.doi.org/10.2147/IJN.S69550 |
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author | Fernandez-Fernandez, Alicia Manchanda, Romila Carvajal, Denny A Lei, Tingjun Srinivasan, Supriya McGoron, Anthony J |
author_facet | Fernandez-Fernandez, Alicia Manchanda, Romila Carvajal, Denny A Lei, Tingjun Srinivasan, Supriya McGoron, Anthony J |
author_sort | Fernandez-Fernandez, Alicia |
collection | PubMed |
description | Near-infrared dyes can be used as theranostic agents in cancer management, based on their optical imaging and localized hyperthermia capabilities. However, their clinical translatability is limited by issues such as photobleaching, short circulation times, and nonspecific biodistribution. Nanoconjugate formulations of cyanine dyes, such as IR820, may be able to overcome some of these limitations. We covalently conjugated IR820 with 6 kDa polyethylene glycol (PEG)-diamine to create a nanoconjugate (IRPDcov) with potential for in vivo applications. The conjugation process resulted in nearly spherical, uniformly distributed nanoparticles of approximately 150 nm diameter and zeta potential −0.4±0.3 mV. The IRPDcov formulation retained the ability to fluoresce and to cause hyperthermia-mediated cell-growth inhibition, with enhanced internalization and significantly enhanced cytotoxic hyperthermia effects in cancer cells compared with free dye. Additionally, IRPDcov demonstrated a significantly longer (P<0.05) plasma half-life, elimination half-life, and area under the curve (AUC) value compared with IR820, indicating larger overall exposure to the theranostic agent in mice. The IRPDcov conjugate had different organ localization than did free IR820, with potential reduced accumulation in the kidneys and significantly lower (P<0.05) accumulation in the lungs. Some potential advantages of IR820-PEG-diamine nanoconjugates may include passive targeting of tumor tissue through the enhanced permeability and retention effect, prolonged circulation times resulting in increased windows for combined diagnosis and therapy, and further opportunities for functionalization, targeting, and customization. The conjugation of PEG-diamine with a near-infrared dye provides a multifunctional delivery vector whose localization can be monitored with noninvasive techniques and that may also serve for guided hyperthermia cancer treatments. |
format | Online Article Text |
id | pubmed-4200025 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-42000252014-10-21 Covalent IR820-PEG-diamine nanoconjugates for theranostic applications in cancer Fernandez-Fernandez, Alicia Manchanda, Romila Carvajal, Denny A Lei, Tingjun Srinivasan, Supriya McGoron, Anthony J Int J Nanomedicine Original Research Near-infrared dyes can be used as theranostic agents in cancer management, based on their optical imaging and localized hyperthermia capabilities. However, their clinical translatability is limited by issues such as photobleaching, short circulation times, and nonspecific biodistribution. Nanoconjugate formulations of cyanine dyes, such as IR820, may be able to overcome some of these limitations. We covalently conjugated IR820 with 6 kDa polyethylene glycol (PEG)-diamine to create a nanoconjugate (IRPDcov) with potential for in vivo applications. The conjugation process resulted in nearly spherical, uniformly distributed nanoparticles of approximately 150 nm diameter and zeta potential −0.4±0.3 mV. The IRPDcov formulation retained the ability to fluoresce and to cause hyperthermia-mediated cell-growth inhibition, with enhanced internalization and significantly enhanced cytotoxic hyperthermia effects in cancer cells compared with free dye. Additionally, IRPDcov demonstrated a significantly longer (P<0.05) plasma half-life, elimination half-life, and area under the curve (AUC) value compared with IR820, indicating larger overall exposure to the theranostic agent in mice. The IRPDcov conjugate had different organ localization than did free IR820, with potential reduced accumulation in the kidneys and significantly lower (P<0.05) accumulation in the lungs. Some potential advantages of IR820-PEG-diamine nanoconjugates may include passive targeting of tumor tissue through the enhanced permeability and retention effect, prolonged circulation times resulting in increased windows for combined diagnosis and therapy, and further opportunities for functionalization, targeting, and customization. The conjugation of PEG-diamine with a near-infrared dye provides a multifunctional delivery vector whose localization can be monitored with noninvasive techniques and that may also serve for guided hyperthermia cancer treatments. Dove Medical Press 2014-10-06 /pmc/articles/PMC4200025/ /pubmed/25336944 http://dx.doi.org/10.2147/IJN.S69550 Text en © 2014 Fernandez-Fernandez et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Fernandez-Fernandez, Alicia Manchanda, Romila Carvajal, Denny A Lei, Tingjun Srinivasan, Supriya McGoron, Anthony J Covalent IR820-PEG-diamine nanoconjugates for theranostic applications in cancer |
title | Covalent IR820-PEG-diamine nanoconjugates for theranostic applications in cancer |
title_full | Covalent IR820-PEG-diamine nanoconjugates for theranostic applications in cancer |
title_fullStr | Covalent IR820-PEG-diamine nanoconjugates for theranostic applications in cancer |
title_full_unstemmed | Covalent IR820-PEG-diamine nanoconjugates for theranostic applications in cancer |
title_short | Covalent IR820-PEG-diamine nanoconjugates for theranostic applications in cancer |
title_sort | covalent ir820-peg-diamine nanoconjugates for theranostic applications in cancer |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200025/ https://www.ncbi.nlm.nih.gov/pubmed/25336944 http://dx.doi.org/10.2147/IJN.S69550 |
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