Obata, H.; Tsuji, A.B.; Sudo, H.; Sugyo, A.; Minegishi, K.; Nagatsu, K.; Ogawa, M.; Zhang, M.-R. In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons. Int. J. Mol. Sci.2021, 22, 4622.
Obata, H.; Tsuji, A.B.; Sudo, H.; Sugyo, A.; Minegishi, K.; Nagatsu, K.; Ogawa, M.; Zhang, M.-R. In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons. Int. J. Mol. Sci. 2021, 22, 4622.
Obata, H.; Tsuji, A.B.; Sudo, H.; Sugyo, A.; Minegishi, K.; Nagatsu, K.; Ogawa, M.; Zhang, M.-R. In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons. Int. J. Mol. Sci.2021, 22, 4622.
Obata, H.; Tsuji, A.B.; Sudo, H.; Sugyo, A.; Minegishi, K.; Nagatsu, K.; Ogawa, M.; Zhang, M.-R. In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons. Int. J. Mol. Sci. 2021, 22, 4622.
Abstract
Due to their short range (2–500 nm), Auger electrons (Auger e-) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Au-ger e-, it remains challenging to maximize the interaction between Auger e- and DNA. To assess the DNA-damaging effect of Auger e- released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [189, 191Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by im-munofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incuba-tion), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by release of Auger e- very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger e-.
Keywords
Auger electron; cisplatin; 191Pt; 189Pt; radio-drug; DNA double-strand break; γH2AX
Subject
Medicine and Pharmacology, Immunology and Allergy
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.