Dual-targeting nanotheranostics for MRI-guided enhanced chemodynamic therapy of hepatoma via regulating the tumor microenvironment.

Chemodynamic therapy (CDT), as a reactive oxygen species (ROS)-based therapeutic modality, has attracted much attention in recent years. However, the insufficient therapeutic effect of CDT is due to the antioxidant system in the tumor microenvironment, such as high levels of glutathione (GSH). In this study, we developed a biological/physical dual-targeting nanotheranostic agent (relaxation rate, r1: 6.3 mM-1 s-1 and r2: 13.11 mM-1 s-1) for enhanced CDT of SMCC-7721 tumors. This nanotheranostic agent is composed of a homologous tumor cell membrane (TCM), magnetic ferric oxide, and manganese oxide and is denoted as FM@TCM nanoparticles (NPs). A favorable effect of in vitro CDT on SMCC-7721 cells (IC50: 20 µg mL-1) is demonstrated, attributed to the Fenton reaction and oxidative stress resulting from the reduction of the GSH level. In vivo T1/T2 magnetic resonance imaging (MRI) confirms that the tumor accumulation of FM@TCM NPs is promoted by concurrent bioactive targeting of the homologous TCM and physico-magnetic targeting of tumor tissues with an external magnetic field. Impressive chemodynamic therapeutic effects on SMCC-7721 tumors are demonstrated through the catalysis of endogenous hydrogen peroxide and depletion of GSH to generate high levels of ROS. Dual-targeting FM@TCM NPs inhibit SMCC-7721 tumor growth (∼90.9%) in vivo without any biotoxicity. This nanotheranostic agent has great potential for use in MRI-guided CDT.

Correction: Wan et al. Correlation between Hypoperfusion Intensity Ratio and Functional Outcome in Large-Vessel Occlusion Acute Ischemic Stroke: Comparison with Multi-Phase CT Angiography. J. Clin. Med. 2022, 11, 5274.

In the published publication [...].

Correlation between Hypoperfusion Intensity Ratio and Functional Outcome in Large-Vessel Occlusion Acute Ischemic Stroke: Comparison with Multi-Phase CT Angiography.

Background and purpose: Previous studies have shown that Hypoperfusion Intensity Ratio (HIR) derived from Perfusion Imaging (PWI) associated with collateral status in large-vessel occlusion (LVO) acute ischemic stroke (AIS) and could predict the rate of collateral flow, speed of infarct growth, and clinical outcome after endovascular treatment (EVT). We hypothesized that HIR derived from CT Perfusion (CTP) imaging could relatively accurately predict the functional outcome in LVO AIS patients receiving different types of treatment. Methods: Imaging and clinical data of consecutive patients with LVO AIS were retrospectively reviewed. Multi-phase CT angiography (mCTA) scoring was performed by 2 blinded neuroradiologists. CTP images were processed using an automatic post-processing analysis software. Correlation between the HIR and the functional outcome was calculated using the Spearman correlation. The efficacy of the HIR and the CTA collateral scores for predicting prognosis were compared. The optimal threshold of the HIR for predicting favorable functional outcome was determined using receiver operating characteristic (ROC) curve analysis. Results: 235 patients with LVO AIS were included. Patients with favorable functional outcome had lower HIR (0.1 [interquartile range (IQR), 0.1−0.2]) vs. 0.4 (IQR, 0.4−0.5)) and higher mCTA collateral scores (3 [IQR, 3−4] vs. 3 [IQR, 2−3]; p < 0.001) along with smaller infarct core volume (2.1 [IQR, 1.0−4.5]) vs. (15.2 [IQR, 5.5−39.3]; p < 0.001), larger mismatch ratio (22.9 [IQR, 11.6−45.6]) vs. (5.8 [IQR, 2.6−14]); p < 0.001), smaller ischemic volume (59.0 [IQR, 29.7−89.2]) vs. (97.5 [IQR, 68.7−142.2]; p < 0.001), and smaller final infarct volume (12.6 [IQR, 7.5−18.4]) vs. (78.9 [IQR, 44.5−165.0]; p < 0.001) than those with unfavorable functional outcome. The HIR was significantly positively correlated with the functional outcome [r = 0.852; 95% confidence interval (CI): 0.813−0.884; p < 0.0001]. The receiver operating characteristic (ROC) analysis showed that the optimal threshold for predicting a favorable functional outcome was HIR ≤ 0.3 [area under the curve (AUC) 0.968; sensitivity 88.89%; specificity 99.21%], which was higher than the mCTA collateral score [AUC 0.741; sensitivity 82.4%; specificity 48.8%]. Conclusions: HIR was associated with the functional outcome of LVO AIS patients, and the correlation coefficient was higher than mCTA collateral score. HIR outperformed mCTA collateral score in predicting functional outcome.