Mitochondria-Targeted Mesoporous Titanium Dioxide Nanoplatform for Synergistic Nitric Oxide Gas-Sonodynamic Therapy of Breast Cancer
Shuting Zuo, Yan Zhang, Zhenyu Wang, Jing Wang Department of Breast Surgery, The Second Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Jing Wang, Department of Breast Surgery, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China,...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2022-03-01
|
| Series: | International Journal of Nanomedicine |
| Subjects: | |
| Online Access: | https://www.dovepress.com/mitochondria-targeted-mesoporous-titanium-dioxide-nanoplatform-for-syn-peer-reviewed-fulltext-article-IJN |
| _version_ | 1818350352392519680 |
|---|---|
| author | Zuo S Zhang Y Wang Z Wang J |
| author_facet | Zuo S Zhang Y Wang Z Wang J |
| author_sort | Zuo S |
| collection | DOAJ |
| description | Shuting Zuo, Yan Zhang, Zhenyu Wang, Jing Wang Department of Breast Surgery, The Second Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Jing Wang, Department of Breast Surgery, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China, Tel/Fax +86 431-81136122, Email wangjing001@jlu.edu.cnBackground: Sonodynamic therapy (SDT) has rapidly advanced as a promising alternative to conventional photodynamic therapy owing to its preferable therapeutic depth. However, single-modal SDT exhibits limited efficacy due to the long-term hypoxia in tumors.Method and Results: To address these issues, we proposed a synergistic SDT strategy that integrates mitochondrial targeting with nitric oxide (NO) gas therapy by using multifunctional nanoplatforms. The nanoplatform, which was named as T-mTNPs@L-Arg, was composed of mesoporous titanium dioxide loaded with the NO donor precursor L-arginine (L-Arg) and modified with triphenyl phosphonium (TPP), a mitochondria-targeting ligand. Therefore, T-mTNPs@L-Arg could efficiently concentrate into mitochondria and release NO gas as well as generate reactive oxygen species (ROS) with ultrasound stimulus. Importantly, the released NO gas exerted multiple synergies with SDT, including inducing NO poisoning, generating more lethal reactive nitrogen species (RNS) by reaction with ROS, and alleviating hypoxia through NO-mediated mitochondrial respiration inhibition. On account of the synergistic effects, T-mTNPs@L-Arg showed an outstanding SDT efficacy and a reduced side effect.Conclusion: This work designed a nanoplatform to integrate mitochondria targeting, SDT and NO gas therapy, providing a new strategy for highly efficient breast cancer therapy.Keywords: mitochondria-targeting, nitric oxide, sonodynamic therapy, titanium dioxide, synergistic |
| first_indexed | 2024-12-13T18:20:29Z |
| format | Article |
| id | doaj.art-0d221882d33544c68cf235f3ef855df6 |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-12-13T18:20:29Z |
| publishDate | 2022-03-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-0d221882d33544c68cf235f3ef855df62022-12-21T23:35:44ZengDove Medical PressInternational Journal of Nanomedicine1178-20132022-03-01Volume 17989100273455Mitochondria-Targeted Mesoporous Titanium Dioxide Nanoplatform for Synergistic Nitric Oxide Gas-Sonodynamic Therapy of Breast CancerZuo SZhang YWang ZWang JShuting Zuo, Yan Zhang, Zhenyu Wang, Jing Wang Department of Breast Surgery, The Second Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Jing Wang, Department of Breast Surgery, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China, Tel/Fax +86 431-81136122, Email wangjing001@jlu.edu.cnBackground: Sonodynamic therapy (SDT) has rapidly advanced as a promising alternative to conventional photodynamic therapy owing to its preferable therapeutic depth. However, single-modal SDT exhibits limited efficacy due to the long-term hypoxia in tumors.Method and Results: To address these issues, we proposed a synergistic SDT strategy that integrates mitochondrial targeting with nitric oxide (NO) gas therapy by using multifunctional nanoplatforms. The nanoplatform, which was named as T-mTNPs@L-Arg, was composed of mesoporous titanium dioxide loaded with the NO donor precursor L-arginine (L-Arg) and modified with triphenyl phosphonium (TPP), a mitochondria-targeting ligand. Therefore, T-mTNPs@L-Arg could efficiently concentrate into mitochondria and release NO gas as well as generate reactive oxygen species (ROS) with ultrasound stimulus. Importantly, the released NO gas exerted multiple synergies with SDT, including inducing NO poisoning, generating more lethal reactive nitrogen species (RNS) by reaction with ROS, and alleviating hypoxia through NO-mediated mitochondrial respiration inhibition. On account of the synergistic effects, T-mTNPs@L-Arg showed an outstanding SDT efficacy and a reduced side effect.Conclusion: This work designed a nanoplatform to integrate mitochondria targeting, SDT and NO gas therapy, providing a new strategy for highly efficient breast cancer therapy.Keywords: mitochondria-targeting, nitric oxide, sonodynamic therapy, titanium dioxide, synergistichttps://www.dovepress.com/mitochondria-targeted-mesoporous-titanium-dioxide-nanoplatform-for-syn-peer-reviewed-fulltext-article-IJNmitochondria-targetingnitric oxidesonodynamic therapytitanium dioxidesynergistic |
| spellingShingle | Zuo S Zhang Y Wang Z Wang J Mitochondria-Targeted Mesoporous Titanium Dioxide Nanoplatform for Synergistic Nitric Oxide Gas-Sonodynamic Therapy of Breast Cancer International Journal of Nanomedicine mitochondria-targeting nitric oxide sonodynamic therapy titanium dioxide synergistic |
| title | Mitochondria-Targeted Mesoporous Titanium Dioxide Nanoplatform for Synergistic Nitric Oxide Gas-Sonodynamic Therapy of Breast Cancer |
| title_full | Mitochondria-Targeted Mesoporous Titanium Dioxide Nanoplatform for Synergistic Nitric Oxide Gas-Sonodynamic Therapy of Breast Cancer |
| title_fullStr | Mitochondria-Targeted Mesoporous Titanium Dioxide Nanoplatform for Synergistic Nitric Oxide Gas-Sonodynamic Therapy of Breast Cancer |
| title_full_unstemmed | Mitochondria-Targeted Mesoporous Titanium Dioxide Nanoplatform for Synergistic Nitric Oxide Gas-Sonodynamic Therapy of Breast Cancer |
| title_short | Mitochondria-Targeted Mesoporous Titanium Dioxide Nanoplatform for Synergistic Nitric Oxide Gas-Sonodynamic Therapy of Breast Cancer |
| title_sort | mitochondria targeted mesoporous titanium dioxide nanoplatform for synergistic nitric oxide gas sonodynamic therapy of breast cancer |
| topic | mitochondria-targeting nitric oxide sonodynamic therapy titanium dioxide synergistic |
| url | https://www.dovepress.com/mitochondria-targeted-mesoporous-titanium-dioxide-nanoplatform-for-syn-peer-reviewed-fulltext-article-IJN |
| work_keys_str_mv | AT zuos mitochondriatargetedmesoporoustitaniumdioxidenanoplatformforsynergisticnitricoxidegassonodynamictherapyofbreastcancer AT zhangy mitochondriatargetedmesoporoustitaniumdioxidenanoplatformforsynergisticnitricoxidegassonodynamictherapyofbreastcancer AT wangz mitochondriatargetedmesoporoustitaniumdioxidenanoplatformforsynergisticnitricoxidegassonodynamictherapyofbreastcancer AT wangj mitochondriatargetedmesoporoustitaniumdioxidenanoplatformforsynergisticnitricoxidegassonodynamictherapyofbreastcancer |