Radiodynamic therapy with CsI(na)@MgO nanoparticles and 5-aminolevulinic acid

• Type of Material: Article
• Authors: Fangchao Jiang, University of Georgia; Chaebin Lee, University of Georgia; Weizhong Zhang, University of Georgia; Wen Jiang, University of Georgia; Zhengwei Cao, University of Georgia; Harrison B Chong, University of Georgia; Wei Yang, University of Georgia; Shuyue Zhan, University of Georgia; Jianwen Li, University of Georgia; Yong Teng, Emory University; Zibo Li, University of North Carolina; Jin Xie, University of Georgia
• Language: English
• Date: 2022-07-16
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12951-022-01537-z
• Title of Journal or Parent Work: JOURNAL OF NANOBIOTECHNOLOGY
• Volume: 20
• Issue: 1
• Start Page: 330
• End Page: 330
• Grant/Funding Information: This work was supported by the National Institute of Biomedical Imaging and Bioengineering (Grant No. R01EB022596 to J.X.), the National Cancer Institute (Grant No. R01CA247769&R01CA257851 to J.X.), and the National Institute of Dental and Craniofacial Research (R01DE028351 to Y.T.).
• Keywords: CANCER; FLUORESCENCE; Science & Technology; Science & Technology - Other Topics; Scintillator; INDUCED PHOTODYNAMIC THERAPY; PROTOPORPHYRIN IX; PHOTOSENSITIZERS; Cancer; Biotechnology & Applied Microbiology; TOXICITY; Photodynamic therapy; ASSAY; Radiation therapy; IN-VITRO; EFFICACY; MGO NANOPARTICLES; Nanoparticles; Life Sciences & Biomedicine; Nanoscience & Nanotechnology
• Research Categories: Health Sciences, Radiology; Chemistry, General; Health Sciences, Oncology

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: [Figure not available: see fulltext.].