There
has been a significant interest in developing proximity-induced
bioorthogonal reactions for nucleic acid detection and imaging, owing
to their high specificity and tunable reaction kinetics. Herein, we
reported the first design of a fluorogenic sensor by coupling a bioorthogonal
reaction with a DNA cascade circuit for precise RNA imaging in live
cells. Two DNA hairpin probes bearing tetrazines or vinyl ether caged
fluorophores were designed and synthesized. Upon target mRNA triggering
catalytic hairpin assembly, the chemical reaction partners were brought
in a spatial proximity to yield high effective concentrations, which
dramatically facilitated the bioorthogonal reaction efficiency to
unmask the vinyl ether group to activate fluorescence. The proposed
fluorogenic sensor was demonstrated to have a high signal-to-noise
ratio up to ∼30 fold and enabled the sensitive detection of
target mRNA with a detection limit of 4.6 pM. Importantly, the fluorogenic
sensor presented low background signals in biological environments
due to the unique “click to release” feature, avoiding
false positive results caused by unspecific degradation. We also showed
that the fluorogenic sensor could accurately image mRNA in live cells
and distinguish the relative mRNA expression levels in both tumor
and normal cells. Benefiting from these significant advantages, our
method provides a useful tool for basic studies of bioorthogonal chemistry
and early clinical diagnosis.
Nanotheranostic platforms integrated with diagnostic and therapeutic functions have been widely developed for tumor medicine. However, the "always-on" nanotheranostic platforms suffer from poor tumor specificity, which may largely restrict therapeutic efficacy and prevent precise theranostics. Here, we develop an in situ transformable pro-nanotheranostic platform (ZnS/Cu 2 O@ZIF-8@PVP) by encapsulating ZnS and Cu 2 O nanoparticles in a metal−organic framework (MOF) nanomaterial of ZIF-8 that allows activable photoacoustic (PA) imaging and synergistic photothermal/chemodynamic therapy (PTT/CDT) of tumors in vivo. It is shown that the pro-nanotheranostic platform gradually decomposes and releases ZnS nanoparticles and Cu + ions in acidic conditions, which spontaneously trigger a cation exchange reaction and synthesize Cu 2 S nanodots in situ with activated PA signals and PTT effects. Moreover, the excessive Cu + ions function as Fenton-like catalysts and catalyze the production of highly reactive hydroxyl radicals ( • OH) for CDT using elevated levels of H 2 O 2 in tumor microenvironments (TMEs). In vivo studies demonstrate that the in situ transformable pro-nanotheranostic platform can specifically image tumors via PA and photothermal imaging and efficiently ablate tumors through synergistic CDT/PTT. Our in situ transformable pro-nanotheranostic platform could provide a new arsenal for precise theranostics in cancer therapy.
Tetrazine-mediated bioorthogonal reactions was rationally coupled with DNA cascade circuits to enable proximal decaging, which allowed the construction of a fluorogenic aptasensor for the accurate and amplified sensing of non-nucleic...
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