The aberrant aggregation of amyloid-β peptide (Aβ) in the brain has been considered as the major pathological hallmark of Alzheimer's diseases (AD). Inhibition of Aβ aggregation is considered as an attractive therapeutic intervention for alleviating amyloid-associated neurotoxicity. Here, we report the near-infrared light (NIR)-induced suppression of Aβ aggregation and reduction of Aβinduced cytotoxicity via porphyrinic metal-organic framework (MOF) PCN-224 nanoparticles. PCN-224 nanoparticles are hydrothermally synthesized by coordinating tetra-kis(4carboxyphenyl)porphyrin (TCPP) ligands with zirconium. The PCN-224 nanoparticles show high photo-oxygenation efficiency, good biocompatibility, and high stability. The study reveals that the porphyrinic MOF-based nanoprobe activated by NIR light could successfully inhibit self-assembly of monomeric Aβ into a β-sheet-rich structure. Furthermore, photoexcited PCN-224 nanoparticles also significantly reduce Aβ-induced cytotoxicity under NIR irradiation.
Here, a novel colorimetric sensing platform for highly selective detection of Fe 3+ in aqueous solutions was developed based on zero-dimensional Zn-MOF-74 [Zn 2 (DOBDC), DOBDC = 2,5-dihydroxyterephthalic acid] nanodots. The first ultrasmall Zn-MOF-74 nanodots with the average size within 10 nm were successfully synthesized by manipulating the initial conditions with a diluted material system. It was found that the ultrasamll MOF nanodots had a highly selective interaction with Fe 3+ and showed a specific blue colorimetric change in aqueous solution. The highly dispersive nature in aqueous solution and high surface-to-volume ratio help MOF-74 nanodots closely interact with the targeted Fe 3+ ions with a low limit of detection of 1.04 μM and a fast response within seconds. Finally, we demonstrate that the selective Fe 3+ sensing mechanism of Zn-MOF-74 nanodots is due to the selective framework disruption and the formation of Fe-DOBDC salt complex with blue color. It is the first report of nanoscale MOF based colorimetric Fe 3+ sensor with low limit of detection (LOD) comparable even to fluorescent MOF based Fe 3+ sensors, which could be easily observed by naked-eye without expensive fluorescence apparatuses. The good colorimetric stability in aqueous environment, low limit of detection, rapid response, and nanosize nature enable this MOF nanodot to be a good Fe 3+ sensing probe for biological and environmental sensing applications.
Increasing evidence has demonstrated that lactate and adenosine triphosphate (ATP) both play important roles in regulating abnormal metabolism in the tumor microenvironment. Herein, an O2 self‐supplying catalytic nanoagent, based on tannic acid (TA)–Fe(III) coordination complexes‐coated perfluorooctyl bromide (PFOB) nanodroplets with lactate oxidases (LOX) loading (PFOB@TA–Fe(III)–LOX, PTFL), is designed for cascade metabolic‐chemodynamic therapy (CDT) by dual‐depletion of lactate and ATP with hydroxyl •OH radicals generation. Benefiting from the catalytic property of loaded LOX and O2 self‐supplying of PFOB nanodroplets, PTFL nanoparticles (NPs) efficiently deplete tumoral lactate for down‐regulation of vascular endothelial growth factor expression and supplement the insufficient endogenous H2O2 . Simultaneously, TA–Fe(III) complexes release Fe(III) ions and TA in response to intracellular up‐regulated ATP in tumor cells followed by TA‐mediated Fe(III)/Fe(II) conversion, leading to the depletion of energy source ATP and the generation of cytotoxic •OH radicals from H2O2. Moreover, TA–Fe(III) complexes provide photoacoustic contrast as imaging guidance to enhance therapeutic accuracy. As a result, PTFL NPs efficiently accumulate in tumors for suppression of tumor growth and show evidence of anti‐angiogenesis and anti‐metastasis effects. This multifunctional nanoagent may provide new insight for targeting abnormal tumor metabolism with the combination of CDT to achieve a synergistic therapeutic effect.
Osteoarthritis
(OA) is a leading cause of chronic pain in the elderly
worldwide. Yet current diagnosis and therapy for OA pain are subjective
and nonspecific with significant adverse effects. Here, we introduced
a theranostic nanoprobe based on molybdenum disulfide nanosheet-coated
gold nanorods (MoS2-AuNR) targeting never growth factor
(NGF), a key player in pain sensation, for photoacoustic pain imaging
and near-infrared (NIR) imaging-guided photothermal analgesic therapy.
MoS2 coating significantly improved the photoacoustic and
photothermal performance of AuNR. Functionalization of MoS2-AuNR nanoprobes by conjugating with NGF antibody enabled active
targeting on painful OA knees in a surgical OA murine model. We observed
that our functional nanoprobes accumulated in the OA knee rather than
the contralateral intact one, and the amount was correlated with the
severity of mechanical allodynia in our mouse model. Under imaging
guidance, NIR-excited photothermal therapy could mitigate mechanical
allodynia and walking imbalance behavior for both subacute and chronic
stages of OA in a preclinical setting. This molecular theranostic
approach enabled us to specifically localize the source of OA pain
and efficiently block peripheral pain transmission.
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