Abstract
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.
Current Pharmaceutical Design
Title:Modular Nanotransporters for Targeted Intracellular Delivery of Drugs: Folate Receptors as Potential Targets
Volume: 21 Issue: 9
Author(s): Tatiana A. Slastnikova, Andrey A. Rosenkranz, Michael R. Zalutsky and Alexander S. Sobolev
Affiliation:
Keywords: Modular nanotransporters, subcellular drug delivery, cell nucleus, receptor overexpression, EGFR, folate receptors, melanocortin receptors, cancer treatment, activated macrophages, atherosclerosis, auger electron emitters, photosensitizers.
Abstract: 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.
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Slastnikova A. Tatiana, Rosenkranz A. Andrey, Zalutsky R. Michael and Sobolev S. Alexander, Modular Nanotransporters for Targeted Intracellular Delivery of Drugs: Folate Receptors as Potential Targets, Current Pharmaceutical Design 2015; 21 (9) . https://dx.doi.org/10.2174/1381612820666141013121032
DOI https://dx.doi.org/10.2174/1381612820666141013121032 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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