Oxidative stress due to Cu 2+ -triggered aggregation of β-amyloid protein (Aβ) and reactive oxygen species (ROS) overexpression in the brain is an important hallmark of early stages of Alzheimer's disease (AD) pathogenesis. The ideal modulator for improving the oxidative stress microenvironment in AD brains should take both Cu 2+ and ROS into consideration, which has been rarely reported.Here, a combined therapeutic strategy was achieved by co-encapsulating superoxide dismutase (SOD) and catalase (CAT) in imine-linked covalent organic frameworks (COFs), which were modified with peptide KLVFF (T5). The nanocomposite SC@COF-T5 exhibited an oxidative stress eradicating ability through ROS elimination and Cu 2+ chelation, combined with the inhibition of Aβ42 monomer aggregation and disaggregation of Aβ42 fibrils. In vivo experiments indicated that SC@COF-T5 with a high blood−brain barrier (BBB) penetration efficiency was effective to reduce Aβ deposition, expression of pro-inflammatory cytokines, ROS levels, and neurologic damage in AD model mice, consequently rescuing memory deficits of AD mice. This work not only confirms the feasibility and merits of the therapeutic strategy regarding multiple targets for treatment of early AD pathogenesis but also opens up a novel direction for imine-linked COFs in biomedical applications.
Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease that is so far incurable with long-term health risks. The high doses and frequent administration for the available RA drug always lead to adverse side effects. Aiming at the obstacles to achieving effective RA treatment, we prepared macrophage cell membrane-camouflaged nanoparticles (M-EC), which were assembled from epigallocatechin gallate (EGCG) and cerium(IV) ions. Due to its geometrical similarity to the active metal sites of a natural antioxidant enzyme, the EC possessed a high scavenge efficiency to various types of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The macrophage cell membrane assisted M-EC in escaping from the immune system, being uptaken by inflammatory cells, and specifically binding IL-1β. After tail vein injection to the collagen-induced arthritis (CIA) mouse model, the M-EC accumulated at inflamed joints and effectively repaired the bone erosion and cartilage damage of rheumatoid arthritis by relieving synovial inflammation and cartilage erosion. It is expected that the M-EC can not only pave a new way for designing metal−phenolic networks with better biological activity but also provide a more biocompatible therapeutic strategy for effective treatment of RA.
Patients with triple-negative breast cancer (TNBC) have
dismal
prognoses due to the lack of therapeutic targets and susceptibility
to lymph node (LN) metastasis. Therefore, it is essential to develop
more effective approaches to identify early TNBC tissues and LNs.
In this work, a magnetic resonance imaging (MRI) contrast agent (Mn-iCOF)
was constructed based on the Mn(II)-chelated ionic covalent organic
framework (iCOF). Because of the porous structure and hydrophilicity,
the Mn-iCOF has a high longitudinal relaxivity (r
1) of 8.02 mM–1 s–1 at 3.0 T. For the tumor-bearing mice, a lower dose (0.02 mmol [Mn]/kg)
of Mn-iCOF demonstrated a higher signal-to-noise ratio (SNR) value
(1.8) and longer retention time (2 h) compared to a 10-fold dose of
commercial Gd-DOTA (0.2 mmol [Gd]/kg). Moreover, the Mn-iCOF can provide
continuous and significant MR contrast for the popliteal LNs within
24 h, allowing for accurate evaluation and dissection of LNs. These
excellent MRI properties of the Mn-iCOF may open new avenues for designing
more biocompatible MRI contrast agents with higher resolutions, particularly
in the diagnosis of TNBC.
Alloy nanoparticles based nanozymes exhibit unique catalytic properties resulted from their tailoring atomic coordination numbers and geometric parameters. The development of ultrafine alloy nanozyme is effective for improving their catalytic...
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