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Pàgina inicial > Articles > Articles publicats > Nanostructure empowers active tumor targeting in ligand-based molecular delivery |
Data: | 2019 |
Resum: | Cell-selective targeting is expected to enhance effectiveness and minimize side effects of cytotoxic agents. Functionalization of drugs or drug nanoconjugates with specific cell ligands allows receptor-mediated selective cell delivery. However, it is unclear whether the incorporation of an efficient ligand into a drug vehicle is sufficient to ensure proper biodistribution upon systemic administration, and also at which extent biophysical properties of the vehicle may contribute to the accumulation in target tissues during active targeting. To approach this issue, structural robustness of self-assembling, protein-only nanoparticles targeted to the tumoral marker CXCR4 is compromised by reducing the number of histidine residues (from six to five) in a histidine-based architectonic tag. Thus, the structure of the resulting nanoparticles, but not of building blocks, is weakened. Upon intravenous injection in animal models of human CXCR4 colorectal cancer, the administered material loses the ability to accumulate in tumor tissue, where it is only transiently found. It instead deposits in kidney and liver. Therefore, precise cell-targeted delivery requires not only the incorporation of a proper ligand that promotes receptor-mediated internalization, but also, unexpectedly, its maintenance of a stable multimeric nanostructure that ensures high ligand exposure and long residence time in tumor tissue. |
Ajuts: | Ministerio de Ciencia e Innovación BIO2016-76063-R Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-229 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-865 Instituto de Salud Carlos III PI18/00650 Instituto de Salud Carlos III PI15/00272 Instituto de Salud Carlos III PIE15/00028 Instituto de Salud Carlos III FI16/00017 Agència de Gestió d'Ajuts Universitaris i de Recerca 2018/FI_B2_00051 Agència de Gestió d'Ajuts Universitaris i de Recerca 2019/FI_B 00352 |
Nota: | Altres ajuts: to EU COST Action CA 17140 and ICREA Academia |
Drets: | Tots els drets reservats. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió acceptada per publicar |
Matèria: | Nanoparticles ; Self-assembling ; Drug delivery systems ; Active targeting ; Protein engineering ; Cell ligands |
Publicat a: | Particle & particle systems characterization, Vol. 36, Issue 11 (November 2019) , art. 1900304, ISSN 1521-4117 |
Postprint 30 p, 1.5 MB |
Figura 1 Arxiu pptx 2.5 MB |
Figura 2 Arxiu pptx 607.9 KB |
Figura 3 Arxiu pptx 773.4 KB |
Figura 4 Arxiu pptx 143.2 KB |