Radioactive (<sup>90</sup>Y) upconversion nanoparticles conjugated with recombinant targeted toxin for synergistic nanotheranostics of cancer.
basic_science · Level V
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- Record sourced from PubMed, PMID 30194234.
- Also identified by DOI 10.1073/pnas.1809258115 and PMC identifier 6166851.
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Abstract
We report combined therapy using upconversion nanoparticles (UCNP) coupled to two therapeutic agents: beta-emitting radionuclide yttrium-90 (<sup>90</sup>Y) fractionally substituting yttrium in UCNP, and a fragment of the exotoxin A derived from <i>Pseudomonas aeruginosa</i> 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 <sup>90</sup>Y- and PE40-induced cytotoxic effects characterized by IC<sub>50</sub> 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<sub>50</sub> = 0.0024 μg/mL. The combined therapy with UCNP-R-T was demonstrated in vivo.
Medical subject headings
- Drug Delivery Systems
- Endotoxins
- Nanoparticles
- Nanotechnology
- Neoplasms
- Radiotherapy