Cytosolic delivery mediated via electrostatic surface binding of protein, virus, or siRNA cargos to pH-responsive core-shell gel particles.
Biomacromolecules
; 10(4): 756-65, 2009 Apr 13.
Article
em En
| MEDLINE
| ID: mdl-19239276
ABSTRACT
We recently described a strategy for intracellular delivery of macromolecules, utilizing pH-responsive "core-shell" structured gel particles. These cross-linked hydrogel particles disrupt endosomes with low toxicity by virtue of physical sequestration of an endosome-disrupting "proton sponge" core inside a nontoxic hydrophilic shell. Here we tested the efficacy of this system for cytosolic delivery of a broad range of macromolecular cargos, and demonstrate the delivery of proteins, whole viral particles, or siRNA oligonucleotides into the cytosol of dendritic cells and epithelial cells via core-shell particles. We assessed the functional impact of particle delivery for vaccine applications and found that cytosolic delivery of protein antigens in dendritic cells via the core-shell particles promotes priming of CD8(+) T-cells at 100-fold lower doses than soluble protein. Functional gene knockdown following delivery of siRNA using the particles was demonstrated in epithelial cells. Based on these findings, these materials may be of interest for a broad range of biomedical applications.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Vírus da Influenza A
/
Ovalbumina
/
Sistemas de Liberação de Medicamentos
/
Citosol
/
RNA Interferente Pequeno
/
Géis
Limite:
Animals
Idioma:
En
Revista:
Biomacromolecules
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos