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

Abstract

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.

UCNP-based Photoluminescent Nanomedicines for Targeted Imaging and Theranostics of Cancer

“…Theranostics, the trend of biomedicine, which implies the creation of supramolecular complexes with diagnostic and therapeutic properties, fully meets its requirements [ 1 , 2 ]. The study of the molecular peculiarities of tumors and the development of nanotechnology have made it possible to create a number of promising agents based on nanomaterials and intended for diagnostics and targeted therapy [ 3 , 4 , 5 ].…”

Nanomedical Devices and Cancer Theranostics

“…Conjugated with folate, they selectively target cancer sites. [117,118] and [120] Mesoporous silica-based hybrid NPs are the best drug carriers because of their large surface area, size, porosity, chemical stability, and biocompatibility. They can incorporate theranostic molecules and magnetic nanocrystals [70] ( Table 2).…”

“…The hybrid anti-cancer systems integrate Yttrium 90 ( 90 Y) betaemitting radionuclides inside of nanocrystalline matrix coated with NIR light upconversion polymer and coupled to recombinant proteins composed of two modules: i) the DARP in module targeting cells overexpressing the HER2 receptor oncomarker ii) the Exotoxin A cytotoxic module inhibiting the synthesis of HER2-positive cell proteins. These nanocomplexes have diagnostic functions and selective drug therapy of cancer cells [120]. Fig.(3).…”

Functionalized Upconversion Nanoparticles for Targeted Labelling of Bladder Cancer Cells

“…To become a multifunctional agent, UCNP need a tumour-targeting unit. Proteins [19,20], folic acid [21] and antibodies [22] were previously used for diagnostic and therapeutic actions of UCNP. Antibodies are preferable as targeting agents, as they will allow adjustment of the affinity of nanoconjugates, depending on the antigen expression of target cells.…”