Photoactive "Bionic Virus" Robustly Elicits the Synergy Anticancer Activity of Immunophotodynamic Therapy.

Coronavirus represents an inspiring model for designing drug delivery systems due to its unique infection machinery mechanism. Herein, we have developed a biomimetic viruslike nanocomplex, termed SDN, for improving cancer theranostics. SDN has a unique core-shell structure consisting of photosensitizer chlorin e6 (Ce6)-loaded nanostructured lipid carrier (CeNLC) (virus core)@poly(allylamine hydrochloride)-functionalized MnO2 nanoparticles (virus spike), generating a virus-mimicking nanocomplex. SDN not only prompted cellular uptake through rough-surface-mediated endocytosis but also achieved mitochondrial accumulation by the interaction of cationic spikes and the anionic mitochondrial surface, leading to mitochondria-specific photodynamic therapy. Meanwhile, SDN could even mediate oxygen generation to relieve tumor hypoxia and, consequently, improve macrophage-associated anticancer immune response. Importantly, SDN served as a robust magnetic resonance imaging (MRI) contrast agent due to the fast release of Mn2+ in the presence of intracellular redox components. We identified that SDN selectively accumulated in tumors and released Mn2+ to generate a 5.71-fold higher T1-MRI signal, allowing for effectively detecting suspected tumors. Particularly, SDN induced synergistic immunophotodynamic effects to eliminate malignant tumors with minimal adverse effects. Therefore, we present a novel biomimetic strategy for improving targeted theranostics, which has a wide range of potential biomedical applications.

Severe COVID-19 pneumonia: Perfusion analysis in correlation with pulmonary embolism and vessel enlargement using dual-energy CT data.

BACKGROUND: Gas exchange in COVID-19 pneumonia is impaired and vessel obstruction has been suspected to cause ventilation-perfusion mismatch. Dual-energy CT (DECT) can depict pulmonary perfusion by regional assessment of iodine uptake. OBJECTIVE: The purpose of this study was the analysis of pulmonary perfusion using dual-energy CT in a cohort of 27 consecutive patients with severe COVID-19 pneumonia. METHOD: We retrospectively analyzed pulmonary perfusion with DECT in 27 consecutive patients (mean age 57 years, range 21-73; 19 men and 8 women) with severe COVID-19 pneumonia. Iodine uptake (IU) in regions-of-interest placed into normally aerated lung, ground-glass opacifications (GGO) and consolidations was measured using a dedicated postprocessing software. Vessel enlargement (VE) within opacifications and presence of pulmonary embolism (PE) was assessed by subjective analysis. Linear mixed models were used for statistical analyses. RESULTS: Compared to normally aerated lung 106/151 (70.2%) opacifications without upstream PE demonstrated an increased IU, 9/151 (6.0%) an equal IU and 36/151 (23.8%) a decreased IU. The estimated mean iodine uptake (EMIU) in opacifications without upstream PE (GGO 1.77 mg/mL; 95%-CI: 1.52-2.02; p = 0.011, consolidations 1.82 mg/mL; 95%-CI: 1.56-2.08, p = 0.006) was significantly higher compared to normal lung (1.22 mg/mL; 95%-CI: 0.95-1.49). In case of upstream PE, EMIU of opacifications (combined GGO and consolidations) was significantly decreased compared to normal lung (0.52 mg/mL; 95%-CI: -0.07-1.12; p = 0.043). The presence of VE in opacifications correlated significantly with iodine uptake (p<0.001). CONCLUSIONS: DECT revealed the opacifications in a subset of patients with severe COVID-19 pneumonia to be perfused non-uniformly with some being hypo- and others being hyperperfused. Mean iodine uptake in opacifications (both ground-glass and consolidation) was higher compared to normally aerated lung except for areas with upstream pulmonary embolism. Vessel enlargement correlated with iodine uptake: In summary, in a cohort of 27 consecutive patients with severe COVID-19 pneumonia, dual-energy CT demonstrated a wide range of iodine uptake in pulmonary ground-glass opacifications and consolidations as a surrogate marker for hypo- and hyperperfusion compared to normally aerated lung. Applying DECT to determine which pathophysiology is predominant might help to tailor therapy to the individual patient´s needs.

Contrast enhanced ultrasonography (CEUS) to detect abdominal microcirculatory disorders in severe cases of COVID-19 infection: First experience.

In the hands of experienced examiners, the contrast enhanced sonography (CEUS) offers the possibility to analyze dynamic microcirculatory disturbances in real time dynamically without any risk for kidneys and thyroid gland even in severe progressing disease bedside. Based on severe COVID-19 infections, first experiences with abdominal CEUS examinations are presented. In the stage of an imminent organ failure with significantly reduced kidney and liver function, CEUS can be used to show a narrowing of the organ-supplying arteries, as well as a delayed capillary filling of vessels near the capsule, a regional reduced parenchymal perfusion or an inflammatory hyperemia with capillary hypercirculation. It is possible to quickly rule out organ infarction and to dynamically record the mesenteric arterial and venous blood flow.