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We report combined therapy using upconversion nanoparticles (UCNP) coupled to two therapeutic agents: beta-emitting radionuclide yttrium-90 (Y) fractionally substituting yttrium in UCNP, and a fragment of the exotoxin A derived from 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 separateY- and PE40-induced cytotoxic effects characterized by IC 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 = 0.0024 μg/mL. The combined therapy with UCNP-R-T was demonstrated in vivo.

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The range of negative characteristic temperatures in temperature dependences of threshold current density of low-threshold (In, Ga)As/(Al, Ga)As quantum dot injection lasers has been observed. A model describing the decrease in threshold current density with temperature at low temperatures is proposed.