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Pàgina inicial > Articles > Articles publicats > A refined cocktailing of pro-apoptotic nanoparticles boosts anti-tumor activity |
Data: | 2020 |
Resum: | A functional 29 amino acid-segment of the helix α5 from the human BAX protein has been engineered for production in recombinant bacteria as self-assembling, GFP-containing fluorescent nanoparticles, which are targeted to the tumoral marker CXCR4. These nanoparticles, of around 34 nm in diameter, show a moderate tumor biodistribution and limited antitumoral effect when systemically administered to mouse models of human CXCR4 colorectal cancer (at 300 μg dose). However, if such BAX nanoparticles are co-administered in cocktail with equivalent nanoparticulate versions of BAK and PUMA proteins at the same total protein dose (300 μg), protein biodistribution and stability in tumor is largely improved, as determined by fluorescence profiles. This fact leads to a potent and faster destruction of tumor tissues when compared to individual pro-apoptotic factors. The analysis and interpretation of the boosted effect, from both the structural and functional sides, offers clues for the design of more efficient nanomedicines and theragnostic agents in oncology based on precise cocktails of human proteins. Statement of significance: Several human pro-apoptotic peptides (namely BAK, BAX and PUMA) have been engineered as self-assembling protein nanoparticles targeted to the tumoral marker CXCR4. The systemic administration of the same final amounts of those materials as single drugs, or as combinations of two or three of them, shows disparate intensities of antitumoral effects in a mouse model of human colorectal cancer, which are boosted in the triple combination on a non-additive basis. The superiority of the combined administration of pro-apoptotic agents, acting at different levels of the apoptotic cascade, opens a plethora of possibilities for the development of effective and selective cancer therapies based on the precise cocktailing of pro-apoptotic nanoparticulate agents. ing Research Center on Bioengineering, Biomaterials and Nanomedicine. |
Ajuts: | Ministerio de Ciencia e Innovación BIO2016-76063-R Instituto de Salud Carlos III PI15/00272 Instituto de Salud Carlos III FI16/00017 Instituto de Salud Carlos III PIE15//00028 Instituto de Salud Carlos III PI18/00650 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-865 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-229 Agència de Gestió d'Ajuts Universitaris i de Recerca 2018/FI_B2_00051 |
Nota: | Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER) (grant PID2019-105416RB-I00 to EV. U COST Action CA 17140. AV received an ICREA ACADEMIA award. Miguel Servet (CP19/00028) |
Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió acceptada per publicar |
Matèria: | Human proteins ; Nanoparticles ; Nanomedicine ; Drug delivery ; Cancer ; Pro-apoptotic factors ; Recombinant protein ; Pro-apoptotic peptide ; Colorectal cancer ; Targeted drug delivery ; Drug cocktail |
Publicat a: | Acta Biomaterialia, Vol. 113 (Sep. 2020) , p. 584-596, ISSN 1878-7568 |
Article. Postprint 23 p, 492.9 KB |
Figura 1 1 p, 574.2 KB |
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Figura 10 1 p, 1.0 MB |
Llegenda de les figures 4 p, 184.4 KB |
Declaració d'importància 1 p, 8.0 KB |