Radioactive (90Y) upconversion nanoparticles conjugated with recombinant targeted toxin for synergistic nanotheranostics of cancer
Guryev E. L., Volodina N. O., Shilyagina N. Y., Gudkov S. V., Balalaeva I. V., Volovetskij A. B., Lyubeshkin A. V., Sen A. V., Ermilov S. A., Vodeneev V. A., Petrov R. V., Zvyagin A. V., Alferov Z. I., Deev S. M.
Proceedings of the National Academy of Sciences of the United States of America
Vol.115, Issue39, P. 9690-9695
Опубликовано: 2018
Тип ресурса: Статья
DOI:10.1073/pnas.1809258115
Аннотация:
We report combined therapy using upconversion nanoparticles (UCNP) coupled to two therapeutic agents: beta-emitting radionuclide yttrium-90 (90Y) 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 90Y- and PE40-induced cytotoxic effects characterized by IC50 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, re
Ключевые слова:
Combined therapy; Nuclear medicine; Targeted therapy; Theranostics; Upconversion nanoparticles
ankyrin; bacterial toxin; epidermal growth factor receptor 2; recombinant protein; upconversion nanoparticle; yttrium 90; ankyrin; endotoxin; epidermal growth factor receptor 2; ERBB2 protein, human; nanoparticle; recombinant protein; yttrium; animal experiment; animal model; Article; breast adenocarcinoma cell line; cellular distribution; controlled study; cytotoxicity; growth inhibition; human; human cell; IC50; in vitro study; in vivo study; malignant neoplasm; mouse; nonhuman; priority journal; protein binding; Pseudomonas aeruginosa; theranostic nanomedicine; adenocarcinoma; breast tumor; diagnostic imaging; drug delivery system; female; metabolism; nanotechnology; neoplasm; procedures; radiotherapy; scintiscanning; tumor cell line; Adenocarcinoma; Ankyrin Repeat; Breast Neoplasms; Cell Line, Tumor; Drug Delivery Systems; Endotoxins; Female; Humans; Nanoparticles; Nanotechnology; Neoplasms; Pseudomonas aeruginosa; Radionuclide Imaging; Radiotherapy; Receptor, ErbB-2; Recombinant P
Язык текста: Английский
ISSN: 1091-6490
Guryev E. L.
Volodina N. O.
Shilyagina N. Y.
Gudkov S. V.
Balalaeva I. V. Irina Vladimirovna 1978-
Volovetskij A. B. Artur Borisovich 1991-
Lyubeshkin A. V.
Sen A. V.
Ermilov S. A.
Vodeneev V. A.
Petrov R. V.
Zvyagin A. V. Andrej Vasilyevich 1961-
Alferov Z. I.
Deev S. M. Sergej Mikhaylovich 1951-
Гурьев Е. Л.
Володина Н. О.
Шилягина Н. Y.
Гудков С. В.
Балалаева И. В. Ирина Владимировна 1978-
Воловецкий А. Б. Артур Борисович 1991-
Любешкин А. В.
Сен А. В.
Ермилов С. А.
Воденеев В. А.
Петров Р. В.
Звягин А. В. Андрей Васильевич 1961-
Алферов З. И.
Деев С. М. Сергей Михайлович 1951-
Radioactive (90Y) upconversion nanoparticles conjugated with recombinant targeted toxin for synergistic nanotheranostics of cancer
Текст визуальный непосредственный
Proceedings of the National Academy of Sciences of the United States of America
Proquest Academic Research Library
Vol.115, Issue39 P. 9690-9695
2018
Статья
Combined therapy Nuclear medicine Targeted therapy Theranostics Upconversion nanoparticles
ankyrin bacterial toxin epidermal growth factor receptor 2 recombinant protein upconversion nanoparticle yttrium 90 ankyrin endotoxin epidermal growth factor receptor 2 ERBB2 protein, human nanoparticle recombinant protein yttrium animal experiment animal model Article breast adenocarcinoma cell line cellular distribution controlled study cytotoxicity growth inhibition human human cell IC50 in vitro study in vivo study malignant neoplasm mouse nonhuman priority journal protein binding Pseudomonas aeruginosa theranostic nanomedicine adenocarcinoma breast tumor diagnostic imaging drug delivery system female metabolism nanotechnology neoplasm procedures radiotherapy scintiscanning tumor cell line Adenocarcinoma Ankyrin Repeat Breast Neoplasms Cell Line, Tumor Drug Delivery Systems Endotoxins Female Humans Nanoparticles Nanotechnology Neoplasms Pseudomonas aeruginosa Radionuclide Imaging Radiotherapy Receptor, ErbB-2 Recombinant P
We report combined therapy using upconversion nanoparticles (UCNP) coupled to two therapeutic agents: beta-emitting radionuclide yttrium-90 (90Y) 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 90Y- and PE40-induced cytotoxic effects characterized by IC50 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, re