Head-to-head comparison of in vitro and in vivo efficacy of pHLIP-conjugated anti-seed gamma peptide nucleic acids.
Cell Rep Phys Sci
; 4(10)2023 Oct 18.
Article
em En
| MEDLINE
| ID: mdl-38144419
ABSTRACT
Gamma peptide nucleic acids (γPNAs) have recently garnered attention in diverse therapeutic and diagnostic applications. Serine and diethylene-glycol-containing γPNAs have been tested for numerous RNA-targeting purposes. Here, we comprehensively evaluated the in vitro and in vivo efficacy of pH-low insertion peptide (pHLIP)-conjugated serine and diethylene-based γPNAs. pHLIP targets only the acidic tumor microenvironment and not the normal cells. We synthesized and parallelly tested pHLIP-serine γPNAs and pHLIP-diethylene glycol γPNAs that target the seed region of microRNA-155, a microRNA that is upregulated in various cancers. We performed an all-atom molecular dynamics simulation-based computational study to elucidate the interaction of pHLIP-γPNA constructs with the lipid bilayer. We also determined the biodistribution and efficacy of the pHLIP constructs in the U2932-derived xenograft model. Overall, we established that the pHLIP-serine γPNAs show superior results in vivo compared with the pHLIP-diethylene glycol-based γPNA.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Cell Rep Phys Sci
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Estados Unidos