A brain tumor-homing tetra-peptide delivers a nano-therapeutic for more effective treatment of a mouse model of glioblastoma.
Nanoscale Horiz
; 5(8): 1213-1225, 2020 07 27.
Article
en En
| MEDLINE
| ID: mdl-32510090
ABSTRACT
Organ-specific cell-penetrating peptides (CPPs) are a class of molecules that can be highly effective at delivering therapeutic cargoes, and they are currently of great interest in cancer treatment strategies. Herein, we describe a new CPP (amino acid sequence serine-isoleucine-tyrosine-valine, or SIWV) that homes to glioblastoma multiforme (GBM) brain tumor tissues with remarkable specificity in vitro and in vivo. The SIWV sequence was identified from an isoform of annexin-A3 (AA3H), a membrane-interacting human protein. The mechanism of intracellular permeation is proposed to follow a caveolin-mediated endocytotic pathway, based on in vitro and in vivo receptor inhibition and genetic knockdown studies. Feasibility as a targeting agent for therapeutics is demonstrated in a GBM xenograft mouse model, where porous silicon nanoparticles (pSiNPs) containing the clinically relevant anticancer drug SN-38 are grafted with SIWV via a poly-(ethylene glycol) (PEG) linker. The formulation shows enhanced in vivo targeting ability relative to a formulation employing a scrambled control peptide, and significant (P < 0.05) therapeutic efficacy relative to free SN-38 in the GBM xenograft animal model.
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Base de datos:
MEDLINE
Asunto principal:
Oligopéptidos
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Portadores de Fármacos
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Glioblastoma
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Péptidos de Penetración Celular
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Irinotecán
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Antineoplásicos
Idioma:
En
Revista:
Nanoscale Horiz
Año:
2020
Tipo del documento:
Article