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Targeted Nanoparticle Photodynamic Diagnosis and Therapy of Colorectal Cancer

Colorectal cancer (CRC) is an aggressive cancer that remains a challenge to diagnose and treat. Photodynamic diagnosis (PDD) and therapy (PDT) are novel alternative techniques, which can enhance early diagnosis, as well as elicit tumor cell death. This is accomplished through photosensitizer (PS) me...

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Autores principales: Simelane, Nokuphila Winifred Nompumelelo, Kruger, Cherie Ann, Abrahamse, Heidi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466279/
https://www.ncbi.nlm.nih.gov/pubmed/34575942
http://dx.doi.org/10.3390/ijms22189779
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author Simelane, Nokuphila Winifred Nompumelelo
Kruger, Cherie Ann
Abrahamse, Heidi
author_facet Simelane, Nokuphila Winifred Nompumelelo
Kruger, Cherie Ann
Abrahamse, Heidi
author_sort Simelane, Nokuphila Winifred Nompumelelo
collection PubMed
description Colorectal cancer (CRC) is an aggressive cancer that remains a challenge to diagnose and treat. Photodynamic diagnosis (PDD) and therapy (PDT) are novel alternative techniques, which can enhance early diagnosis, as well as elicit tumor cell death. This is accomplished through photosensitizer (PS) mediated fluorescence and cytotoxic reactive oxygen species activation upon laser light irradiation excitation at specific low and high range wavelengths, respectively. However, the lack of PS target tumor tissue specificity often hampers these techniques. This study successfully fabricated a bioactive nanoconjugate, ZnPcS(4)-AuNP-S-PEG5000-NH(2)-Anti-GCC mAb (BNC), based upon a polyethylene glycol-gold nanoparticle, which was multi-functionalized with a fluorescent PDT metalated zinc phthalocyanine PS, and specific anti-GCC targeting antibodies, to overcome CRC PDD and PDT challenges. The BNC was found to be stable and showed selectively improved subcellular accumulation within targeted CRC for improved PDD and PDT outcomes in comparison to healthy in vitro cultured cells. Additionally, the BNC reported significantly higher late apoptotic PDT-induced CRC cell death rates (34% ***) when compared to PDT PS administration alone (15% *). These results indicated that the improved PDD and PDT outcomes were due to the specific PS accumulation in CRC cells through nanoparticle carriage and bioactive anti-GCC targeting.
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spelling pubmed-84662792021-09-27 Targeted Nanoparticle Photodynamic Diagnosis and Therapy of Colorectal Cancer Simelane, Nokuphila Winifred Nompumelelo Kruger, Cherie Ann Abrahamse, Heidi Int J Mol Sci Article Colorectal cancer (CRC) is an aggressive cancer that remains a challenge to diagnose and treat. Photodynamic diagnosis (PDD) and therapy (PDT) are novel alternative techniques, which can enhance early diagnosis, as well as elicit tumor cell death. This is accomplished through photosensitizer (PS) mediated fluorescence and cytotoxic reactive oxygen species activation upon laser light irradiation excitation at specific low and high range wavelengths, respectively. However, the lack of PS target tumor tissue specificity often hampers these techniques. This study successfully fabricated a bioactive nanoconjugate, ZnPcS(4)-AuNP-S-PEG5000-NH(2)-Anti-GCC mAb (BNC), based upon a polyethylene glycol-gold nanoparticle, which was multi-functionalized with a fluorescent PDT metalated zinc phthalocyanine PS, and specific anti-GCC targeting antibodies, to overcome CRC PDD and PDT challenges. The BNC was found to be stable and showed selectively improved subcellular accumulation within targeted CRC for improved PDD and PDT outcomes in comparison to healthy in vitro cultured cells. Additionally, the BNC reported significantly higher late apoptotic PDT-induced CRC cell death rates (34% ***) when compared to PDT PS administration alone (15% *). These results indicated that the improved PDD and PDT outcomes were due to the specific PS accumulation in CRC cells through nanoparticle carriage and bioactive anti-GCC targeting. MDPI 2021-09-10 /pmc/articles/PMC8466279/ /pubmed/34575942 http://dx.doi.org/10.3390/ijms22189779 Text en © 2021 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
Simelane, Nokuphila Winifred Nompumelelo
Kruger, Cherie Ann
Abrahamse, Heidi
Targeted Nanoparticle Photodynamic Diagnosis and Therapy of Colorectal Cancer
title Targeted Nanoparticle Photodynamic Diagnosis and Therapy of Colorectal Cancer
title_full Targeted Nanoparticle Photodynamic Diagnosis and Therapy of Colorectal Cancer
title_fullStr Targeted Nanoparticle Photodynamic Diagnosis and Therapy of Colorectal Cancer
title_full_unstemmed Targeted Nanoparticle Photodynamic Diagnosis and Therapy of Colorectal Cancer
title_short Targeted Nanoparticle Photodynamic Diagnosis and Therapy of Colorectal Cancer
title_sort targeted nanoparticle photodynamic diagnosis and therapy of colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466279/
https://www.ncbi.nlm.nih.gov/pubmed/34575942
http://dx.doi.org/10.3390/ijms22189779
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