A Cascade Targeted and Activatable NIR-ⅡNanoprobe for Highly Sensitive Detection of Acute Myeloid Leukemia in an Orthotopic Model

Acute myeloid leukemia(AML)remains a significant concern in modern medicine.Early diagnosis is the key to improving the therapeutic effects of AML.In the present work,a cascade-targeted and activatable NIR-Ⅱ nanoprobe(Ald&A1094@Ag_(2)S)was developed for early detection of AML in an orthotopic model.Upon intravenous injection,Ald&A1094@Ag_(2)S effectively accumulated in bone tissue due to its high affinity for alendronate(Ald)to the bone.Thereafter,the AML microenvironment allowed for the membrane-penetrating peptide TAT(cell‐penetrating peptide(CGRRRQRRKKRG))to be exposed via pH-sensitive hydrazone bond-mediated detaching of bone-targeted ligands,resulting in efficient internalization of nanoprobes in HL60 cells.Endogenous peroxynitrite(ONOO–)in HL60 cells further activated NIR-Ⅱ fluorescence of Ag_(2)S QDs via A1094 oxidation,thereby inhibiting fluorescence resonance energy transfer(FRET).Such a unique cascade-targeted and activatable strategy enables the nanoprobes to only light up the AML lesion region in the bone marrow with negligible background effects,which holds great potential for clinical applications in the future.

PET imaging on neurofunctional changes after optogenetic stimulation in a rat model of panic disorder

Panic disorder (PD) is an acute paroxysmal anxiety disorder with poorly understood pathophysiology. The dorsal periaqueductal gray (dPAG) is involved in the genesis of PD. However, the downstream neurofunctional changes of the dPAG during panic attacks have yet to be evaluated in vivo. In this study, optogenetic stimulation to the dPAG was performed to induce panic-like behaviors, and in vivo positron emission tomography (PET) imaging with ,8F-flurodeoxyglucose (18F-FDG) was conducted to evaluate neurofunctional changes before and after the optogenetic stimulation. Compared with the baseline, post-optogenetic stimulation PET imaging demonstrated that the glucose metabolism significantly increased (P < 0.001) in dPAG, the cuneiform nucleus, the cerebellar lobule, the cingulate cortex, the alveus of the hippocampus, the primary visual cortex, the septohypothalamic nucleus, and the retrosplenial granular cortex but significantly decreased (P < 0.001) in the basal ganglia, the frontal cortex, the forceps minor corpus callosum, the primary somatosensory cortex, the primary motor cortex, the secondary visual cortex, and the dorsal lateral geniculate nucleus. Taken together, these data indicated that in vivo PET imaging can successfully detect downstream neurofunctional changes involved in the panic attacks after optogenetic stimulation to the dPAG.