tretazicar (CB1954)

As cancers have cell-type specific promoters, catalysis can be predisposed to occur in only such tissue.One DEPT modality for mediating SGT is the canonical G-/V-DEPT nitroreductase (NTR)-CB1954 system, which uses E. coli-derived nfsB transgene and a nitroaromatic-containing prodrug...To overcome such drawbacks, we exploit condition-restrictive oxics to provide for the first latent reporter responding to only Type I NTR activity in brain cancer cells upon NsfB haloenzyme presentation via it catalyzing a multimechanistic-mediated modulation to its aptly-tuned energetics under normoxic conditions. The latent reporter displays a manifold fluorescence enhancement in the NIR-I spectral region, thereby having application towards directly confirming (i) nsfB delivery via its presentation, (ii) prodrug activation, and (ii) allowing for its NIRF image-guided surgical removal.

The intranasal delivery of uPA-AuNS-TK-p53-NTR-microRNAs NPs (pAuNS@TK-p53-NTR-miRs) in mice predominantly accumulated in lungs and facilitated ganciclovir and CB1954 prodrug-mediated gene therapy against TNBC lung metastases. This new nanosystem may serve as an adaptable-across-cancer-type, facile, and clinically scalable platform to allow future inhalational suicide gene-miR combination therapy for patients harboring pulmonary metastases.