The review is devoted to a subcellular drug delivery system, modular nanotransporters (MNT) that can penetrate into target
cells and deliver a therapeutic into their subcellular compartments, particularly into the nucleus. The therapeutics which need such type of
delivery belong to two groups: (i) those that exert their effect only when delivered into a certain cell compartment (like DNA delivered
into the nucleus); and (ii) those drugs that are capable of exerting their effect in different parts of the cells, however there can be found a
cell compartment that is the most sensitive to their effect. A particular interest attract such cytotoxic agents as Auger electron emitters
which are known to be ineffective outside the cell nucleus, whereas they possess high cytotoxicity in the vicinity of nuclear DNA through
the induction of non-reparable double-strand DNA breaks. The review discusses main approaches permitting to choose internalizable receptors
permitting both recognition of target cells and penetration into them. Special interest attract folate receptors which become accessible
to blood circulating therapeutics after malignant transformation or on activated macrophages which makes them an attractive target
for both several oncological and inflammatory diseases, like atherosclerosis. In vitro and in vivo experiments demonstrated that MNT is a
promising platform for targeted delivery of different therapeutics into the nuclei of target cells.
Keywords: Modular nanotransporters, subcellular drug delivery, cell nucleus, receptor overexpression, EGFR, folate receptors, melanocortin
receptors, cancer treatment, activated macrophages, atherosclerosis, auger electron emitters, photosensitizers.
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