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Lymph‐Directed Self‐Immolative Nitric Oxide Prodrug for Inhibition of Intractable Metastatic Cancer

There has been a significant clinical demand for lymph‐directed anti‐metastatic therapy as tumor‐draining lymph nodes play pivotal roles in cancer metastasis which accounts for more than 90% of tumor‐related deaths. Despite the high potential of nitric oxide (NO) in anti‐cancer therapy owing to its...

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Detalles Bibliográficos
Autores principales: Kim, Taejeong, Suh, Jeeyeon, Kim, Jihoon, Kim, Won Jong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8922110/
https://www.ncbi.nlm.nih.gov/pubmed/35317221
http://dx.doi.org/10.1002/advs.202101935
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author Kim, Taejeong
Suh, Jeeyeon
Kim, Jihoon
Kim, Won Jong
author_facet Kim, Taejeong
Suh, Jeeyeon
Kim, Jihoon
Kim, Won Jong
author_sort Kim, Taejeong
collection PubMed
description There has been a significant clinical demand for lymph‐directed anti‐metastatic therapy as tumor‐draining lymph nodes play pivotal roles in cancer metastasis which accounts for more than 90% of tumor‐related deaths. Despite the high potential of nitric oxide (NO) in anti‐cancer therapy owing to its biocompatibility and tumor cell‐specific cytotoxicity, the poor stability and lack of target specificity of present NO donors and delivery systems have limited its clinical applications. Herein, a redox‐triggered self‐immolative NO prodrug that can be readily conjugated to various materials containing free thiol groups such as albumin, is reported. The prodrug and its conjugates demonstrate smart release of NO donor via intramolecular cyclization under reductive conditions, followed by spontaneously generating NO in physiological conditions. The albumin‐prodrug conjugate inhibits tumor metastasis by inducing cytotoxicity preferentially on tumor cells after efficiently draining into lymph nodes. This novel prodrug can contribute to the development of on‐demand NO delivery systems for anti‐metastatic therapy and other treatments.
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spelling pubmed-89221102022-03-21 Lymph‐Directed Self‐Immolative Nitric Oxide Prodrug for Inhibition of Intractable Metastatic Cancer Kim, Taejeong Suh, Jeeyeon Kim, Jihoon Kim, Won Jong Adv Sci (Weinh) Research Articles There has been a significant clinical demand for lymph‐directed anti‐metastatic therapy as tumor‐draining lymph nodes play pivotal roles in cancer metastasis which accounts for more than 90% of tumor‐related deaths. Despite the high potential of nitric oxide (NO) in anti‐cancer therapy owing to its biocompatibility and tumor cell‐specific cytotoxicity, the poor stability and lack of target specificity of present NO donors and delivery systems have limited its clinical applications. Herein, a redox‐triggered self‐immolative NO prodrug that can be readily conjugated to various materials containing free thiol groups such as albumin, is reported. The prodrug and its conjugates demonstrate smart release of NO donor via intramolecular cyclization under reductive conditions, followed by spontaneously generating NO in physiological conditions. The albumin‐prodrug conjugate inhibits tumor metastasis by inducing cytotoxicity preferentially on tumor cells after efficiently draining into lymph nodes. This novel prodrug can contribute to the development of on‐demand NO delivery systems for anti‐metastatic therapy and other treatments. John Wiley and Sons Inc. 2022-01-05 /pmc/articles/PMC8922110/ /pubmed/35317221 http://dx.doi.org/10.1002/advs.202101935 Text en © 2022 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Kim, Taejeong
Suh, Jeeyeon
Kim, Jihoon
Kim, Won Jong
Lymph‐Directed Self‐Immolative Nitric Oxide Prodrug for Inhibition of Intractable Metastatic Cancer
title Lymph‐Directed Self‐Immolative Nitric Oxide Prodrug for Inhibition of Intractable Metastatic Cancer
title_full Lymph‐Directed Self‐Immolative Nitric Oxide Prodrug for Inhibition of Intractable Metastatic Cancer
title_fullStr Lymph‐Directed Self‐Immolative Nitric Oxide Prodrug for Inhibition of Intractable Metastatic Cancer
title_full_unstemmed Lymph‐Directed Self‐Immolative Nitric Oxide Prodrug for Inhibition of Intractable Metastatic Cancer
title_short Lymph‐Directed Self‐Immolative Nitric Oxide Prodrug for Inhibition of Intractable Metastatic Cancer
title_sort lymph‐directed self‐immolative nitric oxide prodrug for inhibition of intractable metastatic cancer
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8922110/
https://www.ncbi.nlm.nih.gov/pubmed/35317221
http://dx.doi.org/10.1002/advs.202101935
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