Ternary Nanoparticles with a Sheddable Shell Efficiently Deliver MicroRNA-34a against CD44-Positive Melanoma.
Mol Pharm
; 14(9): 3152-3163, 2017 09 05.
Article
en En
| MEDLINE
| ID: mdl-28759238
ABSTRACT
PEGylation can stabilize drug delivery systems for cancer therapy by creating repulsive interactions with biological components in vivo. While these interactions reduce nonspecific adsorption of drug-loaded particles onto nontarget surfaces, they also inhibit internalization of particles into target cells. To circumvent this so-called "PEG-dilemma", we have developed nanoparticles with a PEG coating that is shed after arrival in target tissue. Positively charged polycation nanoparticles were assembled with microRNA-34a via electrostatic interactions and then coated again via electrostatic interactions with an anionic PEG derivative that separates from the nanoparticle in the acidic tumor microenvironment. The resulting ternary nanoparticles with a sheddable shell have nearly neutral surface charge, which markedly reduces nonspecific adsorption. Shedding the PEG coat enhanced nanoparticle uptake into CD44-positive melanoma cells and promoted microRNA-34a release, which down-regulated CD44 expression and thereby inhibited tumor growth. We conclude that nanocarriers with a sheddable shell show promise for cancer therapy.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Receptores de Hialuranos
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MicroARNs
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Nanopartículas
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Melanoma
Límite:
Animals
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Humans
Idioma:
En
Año:
2017
Tipo del documento:
Article