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Photodynamic Therapy Activity of New Porphyrin-Xylan-Coated Silica Nanoparticles in Human Colorectal Cancer
Abstract
Photodynamic therapy (PDT) using porphyrins has been approved for treatment of several solid tumors due to the generation of cytotoxic reactive oxygen species (ROS). However, low physiological solubility and lack of selectivity towards tumor sites are the main limitations of their clinical use. Nanoparticles are able to spontaneously accumulate in solid tumors through an enhanced permeability and retention (EPR) effect due to leaky vasculature, poor lymphatic drainage, and increased vessel permeability. Herein, we proved the added value of nanoparticle vectorization on anticancer efficacy and tumor-targeting by 5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin (TPPOH). Using 80 nm silica nanoparticles (SNPs) coated with xylan-TPPOH conjugate (TPPOH-X), we first showed very significant phototoxic effects of TPPOH-X SNPs mediated by post-PDT ROS generation and stronger cell uptake in human colorectal cancer cell lines compared to free TPPOH. Additionally, we demonstrated apoptotic cell death induced by TPPOH-X SNPs-PDT and the interest of autophagy inhibition to increase anticancer efficacy. Finally, we highlighted in vivo, without toxicity, elevated anticancer efficacy of TPPOH-X SNPs through improvement of tumor-targeting compared to a free TPPOH protocol. Our work demonstrated for the first time the strong anticancer efficacy of TPPOH in vitro and in vivo and the merit of SNPs vectorization.
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“However, to date, reports on the application of xylan for anti-cancer drug delivery have only investigated ordinary nanocarriers to increase the water dispersibility of hydrophobic drugs and use the enhanced permeability and retention effects of tumors19,20.”
From Combining gut microbiota modulation and chemotherapy by capecitabine-loaded prebiotic nanoparticle improves colorectal cancer therapy (2023) · cites this paper as [20]
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Photodynamic therapy – mechanisms, photosensitizers and combinations
Kwiatkowski, S., Knap, B., Przystupski, D., Saczko, J., Kędzierska, E., Knap-Czop, K., Kotlińska, J., Michel, O., Kotowski, K., & Kulbacka, J. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.07.049 · Cited by 2,173 · cited 1×
“Relative to traditional therapies, PDT has several advantages including non-invasive therapy, non-cytotoxic molecules without light activation, and site-specific light treatment which decreases the side effects, thus accelerating the healing process [8,9].”
BackgroundLi, X., Zhu, F., Jiang, J., Sun, C., Wang, X., Shen, M., Tian, R., Shi, C., Xu, M., Peng, F., et al. (2015) · Cancer Letters · doi:10.1016/j.canlet.2014.11.026 · Cited by 116 · cited 1×
“PDT-induced ROS-generation triggers mitochondrial pore-opening leading to caspase activation and thus induces apoptotic cell death [50,51].”
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Sorted by citations
Lang, T., Zhu, R., Zhu, X., Yan, W., Li, Y., Zhai, Y., Wu, T., Huang, X., Yin, Q., & Li, Y. (2023) · Nature Communications · doi:10.1038/s41467-023-40439-y · Cited by 133
Acetylxylan‐pheophorbide‐a nanoparticles designed for tumor‐targeted photodynamic therapy
Bouramtane, S., Bretin, L., Pinon, A., Leger, D., Liagre, B., Perez, D. D. S., Launay, Y., Brégier, F., Sol, V., & Chaleix, V. (2021) · Journal of Applied Polymer Science · doi:10.1002/app.50799 · Cited by 20
Self-citation
Metadata
- Authors
- Bretin, L., Pinon, A., Bouramtane, S., Ouk, C., Richard, L., Perrin, M.-L., Chaunavel, A., Carrion, C., Bregier, F., Sol, V., Chaleix, V., Leger, D. Y., & Liagre, B.
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2019-09-30
- Volume
- 11
- Issue
- 10
- Pages
- 1474
- ISSN
- 2072-6694
- PMC
- PMC6826978
- Cited by
- 62
- References
- 2
- Language
- en
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- Bretin, L., Pinon, A., Bouramtane, S., Ouk, C., Richard, L., Perrin, M.-L., Chaunavel, A., Carrion, C., Bregier, F., Sol, V., Chaleix, V., Leger, D. Y., & Liagre, B. (2019). Photodynamic Therapy Activity of New Porphyrin-Xylan-Coated Silica Nanoparticles in Human Colorectal Cancer. Cancers. https://doi.org/10.3390/cancers11101474