ИСТИНА

The nucleus of a cancer cell is the target for the most therapeutic anticancer approaches including chemotherapeutics and ionizing radiation. Targeted drug delivery into this cell compartment is a challenging problem, and its successful solution can significantly increase the treatment efficacy and reduce side effects of the delivered therapeutic agents. We developed modular nanotransporters (MNTs), which are a multifunctional platform designed to achieve receptor-specific delivery of short-range therapeutics into the cell nucleus by receptor-mediated endocytosis, endosome escape, and targeted nuclear transport. Now our research is devoted to the development of the MNT platform in tandem with Auger electron emitting 111In for cancer therapy of malignancies with overexpression of receptors for epidermal growth factor, α-melanocyte-stimulating hormone and folate. Gamma-ray emitting 111In, which is extensively used for imaging, is also the source of short range Auger electrons (AE). While exhibiting negligible effect outside the cells, these AE become highly toxic in the vicinity of DNA within the cell nucleus. Our MNT with attached 111In demonstrated high cytotoxicity for cancer cells in vitro and enhancement of animal survival in cancer models in vivo.