Selective CXCR4(+) Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant Ricin
Por:
Diaz, R, Pallares, V, Cano-Garrido, O, Serna, N, Sanchez-Garcia, L, Falgas, A, Pesarrodona, M, Unzueta, U, Sanchez-Chardi, A, Sanchez, JM, Casanova, I, Vazquez, E, Mangues, R, Villaverde, A
Publicada:
27 jun 2018
Resumen:
Under the unmet need of efficient tumor-targeting drugs for oncology, a recombinant version of the plant toxin ricin (the modular protein T22-mRTA-H6) is engineered to self-assemble as protein-only, CXCR4-targeted nanoparticles. The soluble version of the construct self-organizes as regular 11 nm planar entities that are highly cytotoxic in cultured CXCR4(+) cancer cells upon short time exposure, with a determined IC50 in the nanomolar order of magnitude. The chemical inhibition of CXCR4 binding sites in exposed cells results in a dramatic reduction of the cytotoxic potency, proving the receptor-dependent mechanism of cytotoxicity. The insoluble version of T22-mRTA-H6 is, contrarily, moderately active, indicating that free, nanostructured protein is the optimal drug form. In animal models of acute myeloid leukemia, T22-mRTA-H6 nanoparticles show an impressive and highly selective therapeutic effect, dramatically reducing the leukemia cells affectation of clinically relevant organs. Functionalized T22-mRTA-H6 nanoparticles are then promising prototypes of chemically homogeneous, highly potent antitumor nanostructured toxins for precise oncotherapies based on self-mediated intracellular drug delivery.
Filiaciones:
Diaz, R:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
CIBER BBN, Barcelona 08193, Spain
Pallares, V:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, Barcelona 08025, Spain
Cano-Garrido, O:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
CIBER BBN, Barcelona 08193, Spain
Serna, N:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
CIBER BBN, Barcelona 08193, Spain
Sanchez-Garcia, L:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
CIBER BBN, Barcelona 08193, Spain
Falgas, A:
CIBER BBN, Barcelona 08193, Spain
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, Barcelona 08025, Spain
Pesarrodona, M:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
CIBER BBN, Barcelona 08193, Spain
Unzueta, U:
CIBER BBN, Barcelona 08193, Spain
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, Barcelona 08025, Spain
Sanchez-Chardi, A:
Univ Autonoma Barcelona, Serv Microscopia, E-08193 Barcelona, Spain
Sanchez, JM:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Nacl Cordoba, CONICET, IIBYT, ICTA, Ave Velez Sarsfield 1611,X 5016GCA, Cordoba, Argentina
UNC, FCEFyN, Dept Quim, Catedra Quim Biol, Ave Velez Sarsfield 1611,X 5016GCA, Cordoba, Argentina
Casanova, I:
CIBER BBN, Barcelona 08193, Spain
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, Barcelona 08025, Spain
Vazquez, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
CIBER BBN, Barcelona 08193, Spain
Mangues, R:
CIBER BBN, Barcelona 08193, Spain
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, Barcelona 08025, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, Barcelona 08025, Spain
Villaverde, A:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
CIBER BBN, Barcelona 08193, Spain
Open Access
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