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- W2040756711 abstract "Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DCA major challenge in the development of specific and effective targeted treatments is the paradoxical situation: one needs to exploit surface molecular targets for achieving tumor selectivity and nevertheless needs to deliver the therapeutic inside the target cell, e.g. to the cell nucleus because subcellular targeting is generally required for maximizing the therapeutic effect.We created modular nanotransporters (MNT) unifying these 2 contradictory features into one chimeric macromolecule consisting of:- (i) an internalizable ligand module, (ii) a module with nuclear localization sequence, (iii) an endosomolytic module, and (iv) a carrier module. The modules retained their functions within the MNT: they showed high-affinity interactions with target receptors and alpha/beta-importin dimers, and form holes in lipid bilayers at endosomal pH. Anti-cancer therapeutics (photosensitizers, alpha-particle emitting radionuclides) carried by MNT acquired 20-3000 times greater cytotoxicity and cell specificity if compared with free therapeutics.Herein, we have demonstrated in vivo that MNT possess a unique combination of properties compared with other scaffolds for drug delivery such as antibodies, nanoparticles, and liposomes. The MNT can be freeze-dried and reconstituted without loss of activity. Different modules can be inserted into the MNT in order to impart them with a specific set of capabilities; the modules are interchangeable, so they can be adapted for different cell types and/or different subcellular targets. The MNT can be used for the delivery of many types of therapeutics; they demonstrate low toxicity and low induction of delayed type hypersensitivity in mice. The MNT accumulated in murine tumors with high tumor: non-tumor ratios and displayed preferential accumulation in the subcellular compartment of choice, e.g. the cell nucleus. And finally, anti-cancer therapeutics carried by MNT acquired significantly greater cytotoxicity and cell specificity compared with free therapeutics.We think that the MNT represent a new platform for targeted drug delivery that could be applied to the treatment of aberrant cell populations characterized by up regulation of a receptor for which there is a known ligand.Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5485." @default.
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- W2040756711 date "2010-04-15" @default.
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- W2040756711 title "Abstract 5485: Modular nanotransporters: a chimeric multi-functional platform for drug deliveryin vivo" @default.
- W2040756711 doi "https://doi.org/10.1158/1538-7445.am10-5485" @default.
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