RESUMO
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/Cu2O@ZIF-8@PVP) by encapsulating ZnS and Cu2O 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 Cu2S 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 (â¢OH) for CDT using elevated levels of H2O2 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.
Assuntos
Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Humanos , Nanomedicina Teranóstica/métodos , Técnicas Fotoacústicas/métodos , Peróxido de Hidrogênio , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
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 â¼30 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.
Assuntos
Corantes Fluorescentes , RNA , Catálise , DNA/genética , FluorescênciaRESUMO
Tetrazine-mediated bioorthogonal reactions were 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 acid targets in live cells.