文章基本信息

标题：Radioactive (90Y) upconversion nanoparticles conjugated with recombinant targeted toxin for synergistic nanotheranostics of cancer
作者：Evgenii L. Guryev ; Natalia O. Volodina ; Natalia Y. Shilyagina 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2018
卷号：115
期号：39
页码：9690-9695
DOI：10.1073/pnas.1809258115
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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, resulting in IC₅₀ = 0.0024 μg/mL. The combined therapy with UCNP-R-T was demonstrated in vivo.
关键词：theranostics ; targeted therapy ; combined therapy ; nuclear medicine ; upconversion nanoparticles