Radiodynamic therapy with CsI(na)@MgO nanoparticles and 5-aminolevulinic acid
Abstract Background Radiodynamic therapy (RDT) holds the potential to overcome the shallow tissue penetration issue associated with conventional photodynamic therapy (PDT). To this end, complex and sometimes toxic scintillator–photosensitizer nanoconjugates are often used, posing barriers for large-...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-022-01537-z |
| _version_ | 1811278313395585024 |
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| author | Fangchao Jiang Chaebin Lee Weizhong Zhang Wen Jiang Zhengwei Cao Harrison Byron Chong Wei Yang Shuyue Zhan Jianwen Li Yong Teng Zibo Li Jin Xie |
| author_facet | Fangchao Jiang Chaebin Lee Weizhong Zhang Wen Jiang Zhengwei Cao Harrison Byron Chong Wei Yang Shuyue Zhan Jianwen Li Yong Teng Zibo Li Jin Xie |
| author_sort | Fangchao Jiang |
| collection | DOAJ |
| description | Abstract Background Radiodynamic therapy (RDT) holds the potential to overcome the shallow tissue penetration issue associated with conventional photodynamic therapy (PDT). To this end, complex and sometimes toxic scintillator–photosensitizer nanoconjugates are often used, posing barriers for large-scale manufacturing and regulatory approval. Methods Herein, we report a streamlined RDT strategy based on CsI(Na)@MgO nanoparticles and 5-aminolevulinic acid (5-ALA). 5-ALA is a clinically approved photosensitizer, converted to protoporphyrin IX (PpIX) in cancer cells’ mitochondria. CsI(Na)@MgO nanoparticles produce strong ~ 410 nm X-ray luminescence, which matches the Soret band of PpIX. We hypothesize that the CsI(Na)@MgO-and-5-ALA combination can mediate RDT wherein mitochondria-targeted PDT synergizes with DNA-targeted irradiation for efficient cancer cell killing. Because scintillator nanoparticles and photosensitizer are administered separately, the approach forgoes issues such as self-quenching or uncontrolled release of photosensitizers. Results When tested in vitro with 4T1 cells, the CsI(Na)@MgO and 5-ALA combination elevated radiation-induced reactive oxygen species (ROS), enhancing damages to mitochondria, DNA, and lipids, eventually reducing cell proliferation and clonogenicity. When tested in vivo in 4T1 models, RDT with the CsI(Na)@MgO and 5-ALA combination significantly improved tumor suppression and animal survival relative to radiation therapy (RT) alone. After treatment, the scintillator nanoparticles, made of low-toxic alkali and halide elements, were efficiently excreted, causing no detectable harm to the hosts. Conclusions Our studies show that separately administering CsI(Na)@MgO nanoparticles and 5-ALA represents a safe and streamlined RDT approach with potential in clinical translation. Graphical Abstract |
| first_indexed | 2024-04-13T00:33:44Z |
| format | Article |
| id | doaj.art-b9769d6675fd44a7942073622fae707e |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-13T00:33:44Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-b9769d6675fd44a7942073622fae707e2022-12-22T03:10:24ZengBMCJournal of Nanobiotechnology1477-31552022-07-0120111510.1186/s12951-022-01537-zRadiodynamic therapy with CsI(na)@MgO nanoparticles and 5-aminolevulinic acidFangchao Jiang0Chaebin Lee1Weizhong Zhang2Wen Jiang3Zhengwei Cao4Harrison Byron Chong5Wei Yang6Shuyue Zhan7Jianwen Li8Yong Teng9Zibo Li10Jin Xie11Department of Chemistry, University of GeorgiaDepartment of Chemistry, University of GeorgiaDepartment of Chemistry, University of GeorgiaDepartment of Chemistry, University of GeorgiaDepartment of Chemistry, University of GeorgiaDepartment of Chemistry, University of GeorgiaDepartment of Chemistry, University of GeorgiaDepartment of Chemistry, University of GeorgiaDepartment of Chemistry, University of GeorgiaDepartment of Hematology and Medical Oncology & Winship Cancer Institute, Emory University School of MedicineDepartment of Radiology, University of North Carolina at Chapel HillDepartment of Chemistry, University of GeorgiaAbstract Background Radiodynamic therapy (RDT) holds the potential to overcome the shallow tissue penetration issue associated with conventional photodynamic therapy (PDT). To this end, complex and sometimes toxic scintillator–photosensitizer nanoconjugates are often used, posing barriers for large-scale manufacturing and regulatory approval. Methods Herein, we report a streamlined RDT strategy based on CsI(Na)@MgO nanoparticles and 5-aminolevulinic acid (5-ALA). 5-ALA is a clinically approved photosensitizer, converted to protoporphyrin IX (PpIX) in cancer cells’ mitochondria. CsI(Na)@MgO nanoparticles produce strong ~ 410 nm X-ray luminescence, which matches the Soret band of PpIX. We hypothesize that the CsI(Na)@MgO-and-5-ALA combination can mediate RDT wherein mitochondria-targeted PDT synergizes with DNA-targeted irradiation for efficient cancer cell killing. Because scintillator nanoparticles and photosensitizer are administered separately, the approach forgoes issues such as self-quenching or uncontrolled release of photosensitizers. Results When tested in vitro with 4T1 cells, the CsI(Na)@MgO and 5-ALA combination elevated radiation-induced reactive oxygen species (ROS), enhancing damages to mitochondria, DNA, and lipids, eventually reducing cell proliferation and clonogenicity. When tested in vivo in 4T1 models, RDT with the CsI(Na)@MgO and 5-ALA combination significantly improved tumor suppression and animal survival relative to radiation therapy (RT) alone. After treatment, the scintillator nanoparticles, made of low-toxic alkali and halide elements, were efficiently excreted, causing no detectable harm to the hosts. Conclusions Our studies show that separately administering CsI(Na)@MgO nanoparticles and 5-ALA represents a safe and streamlined RDT approach with potential in clinical translation. Graphical Abstracthttps://doi.org/10.1186/s12951-022-01537-zNanoparticlesRadiation therapyPhotodynamic therapyCancerScintillator |
| spellingShingle | Fangchao Jiang Chaebin Lee Weizhong Zhang Wen Jiang Zhengwei Cao Harrison Byron Chong Wei Yang Shuyue Zhan Jianwen Li Yong Teng Zibo Li Jin Xie Radiodynamic therapy with CsI(na)@MgO nanoparticles and 5-aminolevulinic acid Journal of Nanobiotechnology Nanoparticles Radiation therapy Photodynamic therapy Cancer Scintillator |
| title | Radiodynamic therapy with CsI(na)@MgO nanoparticles and 5-aminolevulinic acid |
| title_full | Radiodynamic therapy with CsI(na)@MgO nanoparticles and 5-aminolevulinic acid |
| title_fullStr | Radiodynamic therapy with CsI(na)@MgO nanoparticles and 5-aminolevulinic acid |
| title_full_unstemmed | Radiodynamic therapy with CsI(na)@MgO nanoparticles and 5-aminolevulinic acid |
| title_short | Radiodynamic therapy with CsI(na)@MgO nanoparticles and 5-aminolevulinic acid |
| title_sort | radiodynamic therapy with csi na mgo nanoparticles and 5 aminolevulinic acid |
| topic | Nanoparticles Radiation therapy Photodynamic therapy Cancer Scintillator |
| url | https://doi.org/10.1186/s12951-022-01537-z |
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