A refined cocktailing of pro-apoptotic nanoparticles boosts anti-tumor activity
Por:
Sanchez-Garcia, L, Sala, R, Serna, N, Alamo, P, Parlade, E, Alba-Castellon, L, Volta-Duran, E, Sanchez-Chardi, A, Unzueta, U, Vazquez, E, Mangues, R, Villaverde, A
Publicada:
1 sep 2020
Resumen:
A functional 29 amino acid-segment of the helix a5 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 mu g 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 mu g), 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 selfassembling 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. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Filiaciones:
Sanchez-Garcia, L:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, C Monforte de Lemos 3-5, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
Sala, R:
CIBER Bioingn Biomat & Nanomed CIBER BBN, C Monforte de Lemos 3-5, Madrid 28029, Spain
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau & Josep Carreras Res In, Barcelona 08041, Spain
Serna, N:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, C Monforte de Lemos 3-5, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
Alamo, P:
CIBER Bioingn Biomat & Nanomed CIBER BBN, C Monforte de Lemos 3-5, Madrid 28029, Spain
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau & Josep Carreras Res In, Barcelona 08041, Spain
Parlade, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Alba-Castellon, L:
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau & Josep Carreras Res In, Barcelona 08041, Spain
Volta-Duran, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, C Monforte de Lemos 3-5, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
Sanchez-Chardi, A:
Univ Barcelona, Fac Biol, Dept Biol Evolut Ecol & Ciencies Ambientals, Av Diagonal 643, Barcelona 08028, Spain
Univ Autonoma Barcelona, Serv Microscopia, Barcelona 08193, Spain
Unzueta, U:
CIBER Bioingn Biomat & Nanomed CIBER BBN, C Monforte de Lemos 3-5, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau & Josep Carreras Res In, Barcelona 08041, Spain
Vazquez, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, C Monforte de Lemos 3-5, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
Mangues, R:
CIBER Bioingn Biomat & Nanomed CIBER BBN, C Monforte de Lemos 3-5, Madrid 28029, Spain
Hosp Santa Creu & Sant Pau, Inst Invest Biomed St Pau & Josep Carreras Res In, Barcelona 08041, Spain
Villaverde, A:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, C Monforte de Lemos 3-5, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
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