Reactive oxygen species scavenging and inflammation mitigation enabled by biomimetic prussian blue analogues boycott atherosclerosis

Abstract

Background As one typical cardiovascular disease, atherosclerosis severely endanger people’ life and cause burden to people health and mentality. It has been extensively accepted that oxidative stress and inflammation closely correlate with the evolution of atherosclerotic plaques, and they directly participate in all stages of atherosclerosis. Regarding this, anti-oxidation or anti-inflammation drugs were developed to enable anti-oxidative therapy and anti-inflammation therapy against atherosclerosis. However, current drugs failed to meet clinical demands. Methods Nanomedicine and nanotechnology hold great potential in addressing the issue. In this report, we engineered a simvastatin (Sim)-loaded theranostic agent based on porous manganese-substituted prussian blue (PMPB) analogues. The biomimetic PMPB carrier could scavenge ROS and mitigate inflammation in vitro and in vivo. Especially after combining with Sim, the composite Sim@PMPB NC was expected to regulate the processes of atherosclerosis. As well, Mn2+ release from PMPB was expected to enhance MRI. Results The composite Sim@PMPB NC performed the best in regulating the hallmarks of atherosclerosis with above twofold decreases, typically such as oxidative stress, macrophage infiltration, plaque density, LDL internalization, fibrous cap thickness and foam cell birth, etc. Moreover, H2O2-induced Mn2+ release from PMPB NC in atherosclerotic inflammation could enhance MRI for visualizing plaques. Moreover, Sim@PMPB exhibited high biocompatibility according to references and experimental results. Conclusions The biomimetic Sim@PMPB theranostic agent successfully stabilized atherosclerotic plaques and alleviated atherosclerosis, and also localized and magnified atherosclerosis, which enabled the monitoring of H2O2-associated atherosclerosis evolution after treatment. As well, Sim@PMPB was biocompatible, thus holding great potential in clinical translation for treating atherosclerosis. Graphic abstract

Biomimetic radiosensitizers unlock radiogenetics for local interstitial radiotherapy to activate systematic immune responses and resist tumor metastasis

“…1 c). The ultrasmall size is probably attributed to the BSA-arised confinement effect that can impede MnO 2 overgrowth and coincidently avoid aggregates’ birth [ 27 , 28 ]. An evident characteristic absorbance peak at 200–300 nm corresponding to MnO 2 in the UV–Vis spectrum of MnO 2 -BSA indicates the successful synthesis of MnO 2 -BSA (Fig.…”

“…Thus, numerous efforts have been made to modulate or even reverse these characteristics of the tumor microenvironments, remove treatment resistance and exert robust antitumor activities towards tumor progression, relapse and metastasis by releasing O 2 , elevating ROS half-life [ 15 ], breaking redox balance [ 32 ], blocking migration pathway [ 33 ], etc. MnO 2 -BSA is expected to mitigate the hypoxic microenvironment and liberate the hypoxia-induced imprisonment to IRT since Mn-based nanoparticles have been widely accepted to produce O 2 , produce massive ROS and even monitor treatment process via Fenton-like reactions, similar to Fe-based nanoparticles [ 23 , 28 ]. To investigate how such IRT radiosensitizers-unlocked radiogenetics remodel hypoxic and immunosuppressive microenvironments, tumor microenvironments after different treatments were further investigated to analyze the antitumor principles via immunofluorescence (IF) and immunohistochemical (IHC) staining.…”

Emerging nanobiotechnology-encoded relaxation tuning establishes new MRI modes to localize, monitor and predict diseases

“…In particular, Mn-based NPs can respond to H + and release Mn 2+ after the decomposition of NPs, 84,85 enabling intratumoral signal magnification with a high SNR, precision tumor localization, intratumoral pH detection to predict tumor progression and realizing prognosis evaluation. 84,86 It has been reported that Mn 2+ can amplify the MR signals by interacting with proteins.…”

Simvastatin Inhibits NLRP3 Inflammasome Activation and Ameliorates Lung Injury in Hyperoxia-Induced Bronchopulmonary Dysplasia via the KLF2-Mediated Mechanism

“…In addition, simvastatin demonstrates vascular protective effects by inducing KLF2 expression [ 30 ]. Recent clinical evidence suggests that simvastatin exhibits additional pharmacological effects, such as antioxidant and anti-inflammatory activities, as well as endothelial protection [ 31 ]. Liu et al discovered that simvastatin exerts its therapeutic effect in rats with hepatic ischemia-reperfusion injury via a KLF2-dependent mechanism [ 32 ].…”