| Literature DB >> 30194234 |
Evgenii L Guryev1, Natalia O Volodina1, Natalia Y Shilyagina1, Sergey V Gudkov1,2,3, Irina V Balalaeva1,4, Arthur B Volovetskiy1, Alexander V Lyubeshkin5, Alexey V Sen'6, Sergey A Ermilov6, Vladimir A Vodeneev1, Rem V Petrov7, Andrei V Zvyagin8,4,7,9, Zhores I Alferov10, Sergey M Deyev1,7.
Abstract
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.Entities:
Keywords: combined therapy; nuclear medicine; targeted therapy; theranostics; upconversion nanoparticles
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Year: 2018 PMID： 30194234 PMCID： PMC6166851 DOI： 10.1073/pnas.1809258115
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205