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Date publication
avril 2025
Journal
Biomacromolecules
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SPECHT Alexandre
Tous les auteurs :
Leung HM, Chan HY, Klimezak M, Liu LS, Karam P, Specht A, Bolze F, Lo PK
Lien Pubmed
Résumé
We synthesized new -dialkylaminonitrobiphenyl (ANBP) derivatives, s-ANBP and t-ANBP, functionalized with dimethyltrityl and phosphoramidite groups for incorporation into DNA backbones as photocleavable linkers via solid-phase synthesis. Both derivatives exhibited excellent chemical stability under diverse conditions, including acidic, alkaline, and high-salt environments and elevated temperatures. Their incorporation into DNA influenced duplex stability and antisense oligonucleotide (ASO) dissociation efficiency, depending on the number of ANBP units and adjacent nucleotide deletions. The s-/t-ANBP-conjugated DNA showed efficient one-photon photolysis at 415 nm and enhanced two-photon absorption for extended π-system in -ANBP, with δΦ values of 1.6 GM (740 nm) and 2.7 GM (800 nm). ANBP-conjugated DNA was used to construct a 3D DNA nanocage capable of light-triggered ASO 4625 release, validated by an RNA digestion assay, confirming antisense functionality. This platform demonstrates precise, light-mediated therapeutic delivery and offers potential for broader applications in drug delivery and clinical use.
Référence
Biomacromolecules. 2025 04 24;:
