Turning a Luffa Protein into a Self-Assembled Biodegradable Nanoplatform for Multitargeted Cancer Therapy.
ACS Nano
; 12(11): 11664-11677, 2018 11 27.
Article
em En
| MEDLINE
| ID: mdl-30335959
ABSTRACT
The peptide-derived self-assembly platform has attracted increasing attention for its great potential to develop into multitargeting nanomedicines as well as its inherent biocompatibility and biodegradability. However, their clinical application potentials are often compromised by low stability, weak membrane penetrating ability, and limited functions. Herein, inspired by a natural protein from the seeds of Luffa cylindrica, we engineered via epitope grafting and structure design a hybrid peptide-based nanoplatform, termed Lupbin, which is capable of self-assembling into a stable superstructure and concurrently targeting multiple protein-protein interactions (PPIs) located in cytoplasm and nuclei. We showed that Lupbin can efficiently penetrate cell membrane, escape from early endosome-dependent degradation, and subsequently disassemble into free monomers with wide distribution in cytosol and nucleus. Importantly, Lupbin abrogated tumor growth and metastasis through concurrent blockade of the Wnt/ß-catenin signaling and reactivation of the p53 signaling, with a highly favorable in vivo biosafety profile. Our strategy expands the application of self-assembled nanomedicines into targeting intercellular PPIs, provides a potential nanoplatform with high stability for multitargeted cancer therapy, and likely reinvigorates the development of peptide-based therapeutics for the treatment of different human diseases including cancer.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Proteínas de Plantas
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Neoplasias Cutâneas
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Luffa
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Nanopartículas
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Antineoplásicos Fitogênicos
Limite:
Animals
Idioma:
En
Revista:
ACS Nano
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China