ИСТИНА

A delivery system that could efficiently reach tumor, engage receptors on the cancer cell surface and transport its payload to the cell nucleus would be attractive for maximizing both the specificity and effectiveness of tumor treatment. We [1] created modular nanotransporters (MNT) that are polypeptides containing at least four moieties: a) an internalizable ligand to provide target cell recognition and receptor mediated endocytosis by the cell, b) an endosomolytic module to facilitate escape from endosomes, c) a nuclear localization sequence to allow active transport into the cell nucleus, and d) a carrier domain. MNT can increase in vitro cytotoxicity of photosensitizers [2] and emitters of Auger electrons [3] and α-particles [4] up to a factor of 3,000. MNT selectively accumulate in vivo in cancer cells, with the highest concentration in cell nuclei. Importantly, MNT mediated delivery of photosensitizers resulted in more than 90% longer tumor growth delay and significantly prolonged survival compared with free drug, while producing few if any side effects [5]. Moreover, MNT can deliver a wide spectrum of substances; they possess low toxicity and low immunogenicity in mice; their production and purification is simple and cost effective; it is possible to replace MNT modules to exploit different molecular and subcellular targets and to freeze-dry MNT for prolonged storage.