Self-oxygenation mesoporous MnO2 nanoparticles with ultra-high drug loading capacity for targeted arteriosclerosis therapy

Abstract

Atherosclerosis (AS) is a leading cause of vascular diseases that severely threats the human health due to the lack of efficient therapeutic methods. During the development and progress of AS, macrophages play critical roles, which are polarized into pro-inflammatory M1 phenotype to excrete abundant cytokines and overproduce reactive oxygen species (ROS), and take up excess amount of lipid to form foam cells. In this work, we developed a MnO2-based nanomedicine to re-educate macrophages for targeting AS therapy. The MnO2 was one-pot synthesized under mild condition, showing intrinsic catalase-mimic activity for self-oxygenation by using endogenous H2O2 as substrate. Moreover, the mesoporous structure as well as the abundant metal coordination sites in MnO2 structure facilitated the loading of an anti-AS drug of curcumin (Cur), achieving extraordinarily high drug loading capacity of 54%. Cur displayed a broad spectrum of anti-oxidant and anti-inflammatory capabilities to repolarize M1 macrophages into M2 phenotype, and the catalytic MnO2 recovered the function of lipid efflux transporter to remove lipid from cells by suppressing HIF-1α. Collectively, the nanocarrier and the payload drug functioned as an all-active nanoplatform to synergistically alleviate the syndromes of AS. In ApoE−/− mice model, the nanosystem could significantly prolong the circulation half-life of Cur by sixfold, and enhance drug accumulation in atherosclerotic lesion by 3.5-fold after intravenous injection by virtue of surface hyaluronic acid (HA) modification. As a result, a robust anti-AS efficacy was achieved as evidenced by the decrease of atherosclerotic lesion, plaque area, lipid level. Graphical Abstract

Hemin-incorporating DNA nanozyme enabling catalytic oxygenation and GSH depletion for enhanced photodynamic therapy and synergistic tumor ferroptosis

“…For instance, tedious preparation procedures are required to load and deliver catalase, and the rapid deactivation and degradation of the enzyme is still an intractable problem. Nanozymes, by contrast, are much more stable and cost-effective, and can achieved tumor targeting delivery by rational surface modifications [21,22], while the potential toxicities such as metal poisoning strongly restrict their in vivo applications [23,24]. Moreover, it should also consider the effective PS loading to realize co-delivery, thus making the systems even more complicated.…”

pH-Responsive hyaluronic acid-enveloped ZIF-8 nanoparticles for anti-atherosclerosis therapy

“…The nanoparticles modified with HA on their surfaces should confer unique recognition for the CD44 over-expressed macrophages. 38 To prove this, the macrophages pre-treated with free HA to bind CD44 were investigated, and resulted in the significantly reduced fluorescence in the macrophages, confirming the importance of CD44-mediated target recognition and intracellular uptake (Fig. S3†).…”

CpG-Conjugated Silver Nanoparticles as a Multifunctional Nanomedicine to Promote Macrophage Efferocytosis and Repolarization for Atherosclerosis Therapy

“…AS has been regarded as a chronic inflammatory disease, which is featured with a pro-inflammatory state and dysregulated generation of cytosolic ROS with oxidative stress. − Both of these factors are closely associated with the pathogenesis of AS and strongly aggravate the disease progression, and thus, attenuating systemic inflammation and reducing cytosolic ROS generation to prevent oxidative stress represent reasonable strategies for AS therapy . Fortunately, we have previously demonstrated the robust antioxidative and anti-inflammatory activities of AgNPs, which have been applied in treating chronic inflammatory diseases such as rheumatoid arthritis .…”

“…33−35 Both of these factors are closely associated with the pathogenesis of AS and strongly aggravate the disease progression, 36 and thus, attenuating systemic inflammation and reducing cytosolic ROS generation to prevent oxidative stress represent reasonable strategies for AS therapy. 37 Fortunately, we have previously demonstrated the robust antioxidative and anti-inflammatory activities of AgNPs, which have been applied in treating chronic inflammatory diseases such as rheumatoid arthritis. 19 This is also an important reason we chose AgNPs as carriers to deliver CpG for AS therapy, and the functionalities of such CpG-decorated AgNPs were then examined.…”