Proc Natl Acad Sci U S A, 2018, 115(39):9690-9695

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

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 separate90Y- and PE40-induced cytotoxic effects characterized by IC50140 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.

Guryev EL, Volodina NO, Shilyagina NY, Gudkov SV, Balalaeva IV, Volovetskiy AB, Lyubeshkin AV, Sen AV, Ermilov SA, Vodeneev VA, Petrov RV, Zvyagin AV, Alferov ZI, Deyev SM

IBCH: 6615
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Кол-во цитирований на 08.2020: 18
Данные статьи проверены модераторами 2018-09-25