Radioactive ( 90 Y) upconversion nanoparticles conjugated with recombinant targeted toxin for synergistic nanotheranostics of cancer.

Autor: Guryev EL; The Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 603950 Nizhny Novgorod, Russia., Volodina NO; The Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 603950 Nizhny Novgorod, Russia., Shilyagina NY; The Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 603950 Nizhny Novgorod, Russia., Gudkov SV; The Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 603950 Nizhny Novgorod, Russia.; Department of Experimental Clinical Studies, Moscow Regional Research and Clinical Institute (MONIKI), 129110 Moscow, Russia.; Wave Research Center, Prokhorov General Physics Institute of the Russian Academy of Sciences, 119991 Moscow, Russia., Balalaeva IV; The Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 603950 Nizhny Novgorod, Russia.; Center of Biomedical Engineering, Sechenov University, 119991 Moscow, Russia., Volovetskiy AB; The Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 603950 Nizhny Novgorod, Russia., Lyubeshkin AV; Center of Crystallography and Photonics, Russian Academy of Sciences, 119333 Moscow, Russia., Sen' AV; Scientific and Technical Center 'Amplitude' Ltd., Zelenograd, 124460 Moscow, Russia., Ermilov SA; Scientific and Technical Center 'Amplitude' Ltd., Zelenograd, 124460 Moscow, Russia., Vodeneev VA; The Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 603950 Nizhny Novgorod, Russia., Petrov RV; M. M. Shemyakin & Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia., Zvyagin AV; The Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 603950 Nizhny Novgorod, Russia; andrei.zvyagin@mq.edu.au zhores.alferov@ras.ru.; Center of Biomedical Engineering, Sechenov University, 119991 Moscow, Russia.; M. M. Shemyakin & Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.; Australian Research Council Centre of Excellence for Nanoscale Biophotonics, Macquarie University, Sydney, NSW 2109, Australia., Alferov ZI; Nanotechnology Research and Education Centre of Russian Academy of Sciences, St. Petersburg Academic University, 194021 St. Petersburg, Russia andrei.zvyagin@mq.edu.au zhores.alferov@ras.ru., Deyev SM; The Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 603950 Nizhny Novgorod, Russia.; M. M. Shemyakin & Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
Jazyk: angličtina
Zdroj: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 Sep 25; Vol. 115 (39), pp. 9690-9695. Date of Electronic Publication: 2018 Sep 07.
DOI: 10.1073/pnas.1809258115
Abstrakt: We report combined therapy using upconversion nanoparticles (UCNP) coupled to two therapeutic agents: beta-emitting radionuclide yttrium-90 ( 90 Y) fractionally substituting yttrium in UCNP, and a fragment of the exotoxin A derived from Pseudomonas aeruginosa genetically fused with a targeting designed ankyrin repeat protein (DARPin) specific to HER2 receptors. The resultant hybrid complex UCNP-R-T was tested using human breast adenocarcinoma cells SK-BR-3 overexpressing HER2 receptors and immunodeficient mice, bearing HER2-positive xenograft tumors. The photophysical properties of UCNPs enabled background-free imaging of the UCNP-R-T distribution in cells and animals. Specific binding and uptake of UCNP complexes in SK-BR-3 cells was observed, with separate 90 Y- and PE40-induced cytotoxic effects characterized by IC 50 140 μg/mL (UCNP-R) and 5.2 μg/mL (UCNP-T), respectively. When both therapeutic agents were combined into UCNP-R-T, the synergetic effect increased markedly, ∼2200-fold, resulting in IC 50 = 0.0024 μg/mL. The combined therapy with UCNP-R-T was demonstrated in vivo.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE