Theranostic approach is currently among the fastest growing trends in cancer treatment. It implies the creation of multifunctional agents for simultaneous precise diagnosis and targeted impact on tumor cells. Upconversion nanoparticles (UCNP) are inorganic nanomaterial able of photoluminescence in visible and NIR spectral regions when irradiated with longer wavelengths of light. We aimed at creation of theranostic UCNP-based nanoplatforms combining photoluminescence with ability of targeted labeling of cancer cells and treating them with recombinant toxins and radioactive beta-emitting isotope. We have assembled several types of multifunctional UCNP-based nanoplatforms selective to HER2 receptor overexpressed by cancer cells of many types. The choice of coating polymer and mode of assembly allowed tuning of nanoplatforms charge and colloid stability. Effective cancer cell labeling with obtained nanoplatforms was confirmed both in vitro and in vivo. Of importance, combined action of anticancer toxin (recombinant form of pseudomonas exotoxin A) and beta-emitting isotope (yttrium-90) resulted in very strongly expressed synergistic effect, probably, due to protein synthesis arrest and impeded work of antioxidant and DNA-repair system. Embedment of yttrium-90 in the crystalline core of UCNP prevents spreading of its decay products throughout the body, thus, decreasing the risk of undesired side effects. In an animal study, UCNP-based theranostic nanoplatforms provided visualization of xenograft HER2 expressing tumors and demonstrated their potency in cancer growth inhibition. Moreover, in a model of intraperitoneal metastasis, the treatment with UCNP-nanoplatforms lead to significantly reduced number of the formed metastatic nodes. We believe that UCNP-based theranostic nanoplatforms can be considered as a promising agent for diagnosis and treatment of cancers. The demonstrated potency of combined targeted and radiopharmaceutical agents in one platform evidences the potential of the approach for further anticancer drug development. This work was financially supported by the Ministry of Science and Higher Education of the Russian Federation (project No. 075-15-2020-927).
Irina V. Balalaeva is an associate professor at Biophysics Department and the principal investigator at Laboratory of Optical Theranostics, Institute of Biology and Biomedicine, Lobachevsky University, Russia. Her fields of interests include application of photoluminescent nanoparticles in optical diagnosis and treatment of cancer; targeted therapy; photodynamic therapy; cancer cell biology; 3D in vitro cancer models; role of microenvironment in carcinogenesis and tumor resistance to treatment.
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