A novel nucleolin-binding peptide for Cancer Theranostics.
Theranostics
; 10(20): 9153-9171, 2020.
Article
en En
| MEDLINE
| ID: mdl-32802184
ABSTRACT
Background:
Cancer-specific ligands have been of great interest as pharmaceutical carriers due to the potential for site-specific delivery. In particular, cancer-specific peptides have many advantages over nanoparticles and antibodies, including high biocompatibility, low immunogenicity, and the formation of nontoxic metabolites. The goal of the present study was the development of a novel cancer-specific ligand.Methods:
Cancer-specific peptide ligands were screened using a one-bead-one-compound (OBOC) combinatorial method combined with a multiple-antigen-peptide (MAP) synthesis method. The specificity of the peptide ligands toward cancer cells was tested in vitro using a whole-cell binding assay, flow cytometry, and fluorescence confocal microscopy. The tissue distribution profile and therapeutic efficacy of a paclitaxel (PTX)-conjugated peptide ligand was assessed in vivo using xenograft mouse models.Results:
We discovered that AGM-330 specifically bound to cancer cells in vitro and in vivo. Treatment with PTX-conjugated AGM-330 dramatically inhibited cancer cell growth in vitro and in vivo compared to treatment with PTX alone. The results of pull-down assay and LC-MS/MS analyses showed that membrane nucleolin (NCL) was the target protein of AGM-330. Although NCL is known as a nuclear protein, we observed that it was overexpressed on the membranes of cancer cells. In particular, membrane NCL neutralization inhibited growth in cancer cells in vitro.Conclusions:
In summary, our findings indicated that NCL-targeting AGM-330 has great potential for use in cancer diagnosis and targeted drug delivery in cancer therapy.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos
/
Fosfoproteínas
/
Proteínas de Unión al ARN
/
Paclitaxel
/
Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Theranostics
Año:
2020
Tipo del documento:
Article