Engineering non-antibody human proteins as efficient scaffolds for selective, receptor-targeted drug delivery
Por:
Serna, N, Pallares, V, Unzueta, U, Garcia-Leon, A, Volta-Duran, E, Sanchez-Chardi, A, Parlade, E, Rueda, A, Casanova, I, Falgas, A, Alba-Castellon, L, Sierra, J, Villaverde, A, Vazquez, E, Mangues, R
Publicada:
1 mar 2022
Ahead of Print:
1 feb 2022
Resumen:
Self-assembling non-immunoglobulin scaffold proteins are a promising class of nanoscale carriers for drug delivery and interesting alternatives to antibody-based carriers that are not sufficiently efficient in systemic administration. To exploit their potentialities in clinics, protein scaffolds need to be further tailored to confer appropriate targeting and to overcome their potential immunogenicity, short half-life in plasma and proteolytic degradation. We have here engineered three human scaffold proteins as drug carrier nanoparticles to target the cytokine receptor CXCR4, a tumoral cell surface marker of high clinical relevance. The capability of these scaffolds for the selective delivery of Monomethyl auristatin E has been comparatively evaluated in a disseminated mouse model of human, CXCR4(+) acute myeloid leukemia. Monomethyl auristatin E is an ultra-potent anti-mitotic drug used against a range of hematological neoplasias, which because of its high toxicity is not currently administered as a free drug but as payload in antibody-drug conjugates. The protein nanoconjugates generated here offer a collective strength of simple manufacturing process, high proteolytic and structural stability and multivalent ligand receptor interactions that result in a highly efficient and selective delivery of the payload drug and in a potent anticancer effect. The approach shown here stresses this class of human scaffold proteins as promising alternatives to antibodies for targeted drug delivery in the rapidly evolving drug development landscape.
Filiaciones:
Serna, N:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingn Biomateri Nanomed CIBER BBN, Madrid, Spain
Univ Autonoma Barcelona, Nanoligent SL Edifici Eureka, Barcelona 08193, Spain
Pallares, V:
CIBER Bioingn Biomateri Nanomed CIBER BBN, Madrid, Spain
Biomed Res Inst Sant Pau IIB Sant Pau, St Antoni M Claret 167, Barcelona 08025, Spain
Josep Carreras Leukaemia Res Inst, IJC Campus St Pau, Barcelona 08025, Spain
Unzueta, U:
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingn Biomateri Nanomed CIBER BBN, Madrid, Spain
Biomed Res Inst Sant Pau IIB Sant Pau, St Antoni M Claret 167, Barcelona 08025, Spain
Josep Carreras Leukaemia Res Inst, IJC Campus St Pau, Barcelona 08025, Spain
Garcia-Leon, A:
CIBER Bioingn Biomateri Nanomed CIBER BBN, Madrid, Spain
Biomed Res Inst Sant Pau IIB Sant Pau, St Antoni M Claret 167, Barcelona 08025, Spain
Josep Carreras Leukaemia Res Inst, IJC Campus St Pau, Barcelona 08025, Spain
Volta-Duran, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingn Biomateri Nanomed CIBER BBN, Madrid, Spain
Sanchez-Chardi, A:
Univ Autonoma Barcelona, Serv Microscopia, Barcelona 08193, Spain
Univ Barcelona, Dept Biol Evolutiva Ecol & Ciencies Ambientals, Fac Biol, Barcelona 08028, Spain
Parlade, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingn Biomateri Nanomed CIBER BBN, Madrid, Spain
Rueda, A:
CIBER Bioingn Biomateri Nanomed CIBER BBN, Madrid, Spain
Biomed Res Inst Sant Pau IIB Sant Pau, St Antoni M Claret 167, Barcelona 08025, Spain
Josep Carreras Leukaemia Res Inst, IJC Campus St Pau, Barcelona 08025, Spain
Casanova, I:
CIBER Bioingn Biomateri Nanomed CIBER BBN, Madrid, Spain
Biomed Res Inst Sant Pau IIB Sant Pau, St Antoni M Claret 167, Barcelona 08025, Spain
Josep Carreras Leukaemia Res Inst, IJC Campus St Pau, Barcelona 08025, Spain
Falgas, A:
CIBER Bioingn Biomateri Nanomed CIBER BBN, Madrid, Spain
Biomed Res Inst Sant Pau IIB Sant Pau, St Antoni M Claret 167, Barcelona 08025, Spain
Josep Carreras Leukaemia Res Inst, IJC Campus St Pau, Barcelona 08025, Spain
Alba-Castellon, L:
CIBER Bioingn Biomateri Nanomed CIBER BBN, Madrid, Spain
Biomed Res Inst Sant Pau IIB Sant Pau, St Antoni M Claret 167, Barcelona 08025, Spain
Josep Carreras Leukaemia Res Inst, IJC Campus St Pau, Barcelona 08025, Spain
Sierra, J:
Josep Carreras Leukaemia Res Inst, IJC Campus St Pau, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona 08025, Spain
Villaverde, A:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingn Biomateri Nanomed CIBER BBN, Madrid, Spain
Vazquez, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingn Biomateri Nanomed CIBER BBN, Madrid, Spain
Mangues, R:
CIBER Bioingn Biomateri Nanomed CIBER BBN, Madrid, Spain
Biomed Res Inst Sant Pau IIB Sant Pau, St Antoni M Claret 167, Barcelona 08025, Spain
Josep Carreras Leukaemia Res Inst, IJC Campus St Pau, Barcelona 08025, Spain
Open Access
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