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Novel Pyropheophorbide Phosphatydic Acids Photosensitizer Combined EGFR siRNA Gene Therapy for Head and Neck Cancer Treatment

This study combined two novel nanomedicines, a novel LCP Pyro PA photodynamic therapy (PDT) and LCP EGFR siRNA gene therapy, to treat head and neck cancer. A novel photosensitizer, pyropheophorbide phosphatydic acids (Pyro PA), was first modified into Lipid-Calcium phosphate nanoparticles named LCP...

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Autores principales: Yeh, Chia-Hsien, Chen, Juan, Zheng, Gang, Huang, Leaf, Hsu, Yih-Chih
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470636/
https://www.ncbi.nlm.nih.gov/pubmed/34575510
http://dx.doi.org/10.3390/pharmaceutics13091435
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author Yeh, Chia-Hsien
Chen, Juan
Zheng, Gang
Huang, Leaf
Hsu, Yih-Chih
author_facet Yeh, Chia-Hsien
Chen, Juan
Zheng, Gang
Huang, Leaf
Hsu, Yih-Chih
author_sort Yeh, Chia-Hsien
collection PubMed
description This study combined two novel nanomedicines, a novel LCP Pyro PA photodynamic therapy (PDT) and LCP EGFR siRNA gene therapy, to treat head and neck cancer. A novel photosensitizer, pyropheophorbide phosphatydic acids (Pyro PA), was first modified into Lipid-Calcium phosphate nanoparticles named LCP Pyro PA NPs, and targeted with aminoethylanisamide as a novel PDT photosensitizer. EGFR siRNA was encapsulated into LCP NPs to silence EGFR expression. Measured sizes of LCP EGFR siRNA NPs and LCP Pyro-PA NPs were 34.9 ± 3.0 and 20 nm respectively, and their zeta potentials were 51.8 ± 1.8 and 52.0 ± 7.6 mV respectively. In vitro studies showed that EGFR siRNA was effectively knocked down after photodynamic therapy (PDT) with significant inhibition of cancer growth. SCC4 or SAS xenografted nude mice were used to verify therapeutic efficacy. The LCP Control siRNA+PDT group of SCC4 and SAS showed significantly reduced tumor volume compared to the phosphate buffered saline (PBS) group. In the LCP-EGFR siRNA+LCP Pyro PA without light group and LCP EGFR siRNA + PBS with light group, SCC4 and SAS tumor volumes were reduced by ~140% and ~150%, respectively, compared to the PBS group. The LCP EGFR siRNA+PDT group of SCC4 and SAS tumor volumes were reduced by ~205% and ~220%, respectively, compared to the PBS group. Combined therapy showed significant tumor volume reduction compared to PBS, control siRNA, or PDT alone. QPCR results showed EGFR expression was significantly reduced after treatment with EGFR siRNA with PDT in SCC4 and SAS compared to control siRNA or PDT alone. Western blot results confirmed decreased EGFR protein expression in the combined therapy group. No toxic results were found in serum biomarkers. No inflammatory factors were found in heart, liver and kidney tissues. Results suggest that the novel LCP Pyro PA mediated PDT combined with LCP siEGFR NPs could be developed in clinical modalities for treating human head and neck cancer in the future.
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spelling pubmed-84706362021-09-27 Novel Pyropheophorbide Phosphatydic Acids Photosensitizer Combined EGFR siRNA Gene Therapy for Head and Neck Cancer Treatment Yeh, Chia-Hsien Chen, Juan Zheng, Gang Huang, Leaf Hsu, Yih-Chih Pharmaceutics Article This study combined two novel nanomedicines, a novel LCP Pyro PA photodynamic therapy (PDT) and LCP EGFR siRNA gene therapy, to treat head and neck cancer. A novel photosensitizer, pyropheophorbide phosphatydic acids (Pyro PA), was first modified into Lipid-Calcium phosphate nanoparticles named LCP Pyro PA NPs, and targeted with aminoethylanisamide as a novel PDT photosensitizer. EGFR siRNA was encapsulated into LCP NPs to silence EGFR expression. Measured sizes of LCP EGFR siRNA NPs and LCP Pyro-PA NPs were 34.9 ± 3.0 and 20 nm respectively, and their zeta potentials were 51.8 ± 1.8 and 52.0 ± 7.6 mV respectively. In vitro studies showed that EGFR siRNA was effectively knocked down after photodynamic therapy (PDT) with significant inhibition of cancer growth. SCC4 or SAS xenografted nude mice were used to verify therapeutic efficacy. The LCP Control siRNA+PDT group of SCC4 and SAS showed significantly reduced tumor volume compared to the phosphate buffered saline (PBS) group. In the LCP-EGFR siRNA+LCP Pyro PA without light group and LCP EGFR siRNA + PBS with light group, SCC4 and SAS tumor volumes were reduced by ~140% and ~150%, respectively, compared to the PBS group. The LCP EGFR siRNA+PDT group of SCC4 and SAS tumor volumes were reduced by ~205% and ~220%, respectively, compared to the PBS group. Combined therapy showed significant tumor volume reduction compared to PBS, control siRNA, or PDT alone. QPCR results showed EGFR expression was significantly reduced after treatment with EGFR siRNA with PDT in SCC4 and SAS compared to control siRNA or PDT alone. Western blot results confirmed decreased EGFR protein expression in the combined therapy group. No toxic results were found in serum biomarkers. No inflammatory factors were found in heart, liver and kidney tissues. Results suggest that the novel LCP Pyro PA mediated PDT combined with LCP siEGFR NPs could be developed in clinical modalities for treating human head and neck cancer in the future. MDPI 2021-09-09 /pmc/articles/PMC8470636/ /pubmed/34575510 http://dx.doi.org/10.3390/pharmaceutics13091435 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
Yeh, Chia-Hsien
Chen, Juan
Zheng, Gang
Huang, Leaf
Hsu, Yih-Chih
Novel Pyropheophorbide Phosphatydic Acids Photosensitizer Combined EGFR siRNA Gene Therapy for Head and Neck Cancer Treatment
title Novel Pyropheophorbide Phosphatydic Acids Photosensitizer Combined EGFR siRNA Gene Therapy for Head and Neck Cancer Treatment
title_full Novel Pyropheophorbide Phosphatydic Acids Photosensitizer Combined EGFR siRNA Gene Therapy for Head and Neck Cancer Treatment
title_fullStr Novel Pyropheophorbide Phosphatydic Acids Photosensitizer Combined EGFR siRNA Gene Therapy for Head and Neck Cancer Treatment
title_full_unstemmed Novel Pyropheophorbide Phosphatydic Acids Photosensitizer Combined EGFR siRNA Gene Therapy for Head and Neck Cancer Treatment
title_short Novel Pyropheophorbide Phosphatydic Acids Photosensitizer Combined EGFR siRNA Gene Therapy for Head and Neck Cancer Treatment
title_sort novel pyropheophorbide phosphatydic acids photosensitizer combined egfr sirna gene therapy for head and neck cancer treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470636/
https://www.ncbi.nlm.nih.gov/pubmed/34575510
http://dx.doi.org/10.3390/pharmaceutics13091435
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