Single-Spin Dirac Fermion and Chern Insulator Based on Simple Oxides

It is highly desirable to combine recent advances in the topological quantum phases with technologically relevant materials. Chromium dioxide (CrO₂) is a half-metallic material, widely used in high-end data storage applications. Using first-principles calculations, we show that a novel class of half semimetallic Dirac electronic phase emerges at the interface CrO₂ with TiO₂ in both thin film and superlattice configurations, with four spin-polarized Dirac points in momentum-space (<b><i>k</i></b>-space) band structure. When the spin and orbital degrees of freedom are allowed to couple, the CrO₂/TiO₂ superlattice becomes a Chern insulator without external fields or additional doping. With topological gaps equivalent to 43 K and a Chern number ±2, the ensuing quantization of Hall conductance to ±2<i>e</i>²/<i>h</i> will enable potential development of these highly industrialized oxides for applications in topologically high fidelity data storage and energy-efficient electronic and spintronic devices

Ultrasmall Paramagnetic Iron Oxide Nanoprobe Targeting Epidermal Growth Factor Receptor for In Vivo Magnetic Resonance Imaging of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a common worldwide cancer that is rising rapidly in incidence. MRI is a powerful noninvasive imaging modality for HCC detection, but lack of specific contrast agents limits visualization of small tumors. EGFR is frequently overexpressed in HCC and is a promising target. Peptides have fast binding kinetics, short circulatory half-life, low imaging background, high vascular permeability, and enhanced tissue diffusion for deep tumor penetration. We demonstrate a peptide specific for EGFR labeled with an ultrasmall paramagnetic iron oxide (UPIO) nanoparticle with 3.5 nm dimensions to target HCC using T₁-weighted MRI. We modified the hydrophobic core with oleic acid and capped with PEGylated phospholipids DSPE-PEG and DSPE-PEG-Mal. The EGFR peptide is attached via thioether-mediated conjugation of a GGGSC linker to the maleimide-terminated phospholipids. On in vivo MR images of HCC xenograft tumors, we observed peak nanoprobe uptake at 2 h post-injection followed by a rapid return to baseline by ∼24 h. We measured significantly greater MR signal in tumor with the targeted nanoprobe versus scrambled peptide, blocked peptide, and Gadoteridol. Segmented regions on MR images support rapid renal clearance. No significant difference in animal weight, necropsy, hematology, and chemistry was found between treatment and control groups at one month post-injection. Our nanoprobe based on an EGFR specific peptide labeled with UPIO designed for high stability and biocompatibility showed rapid tumor uptake and systemic clearance to demonstrate safety and promise for clinical translation to detect early HCC

Multiplexed Targeting of Barrett’s Neoplasia with a Heterobivalent Ligand: Imaging Study on Mouse Xenograft in Vivo and Human Specimens ex Vivo

Esophageal adenocarcinoma (EAC) is a molecularly heterogeneous disease that is rising rapidly in incidence and has poor prognosis. We developed a heterobivalent peptide to target detection of early Barrett’s neoplasia by combining monomer heptapeptides specific for either EGFR or ErbB2 in a heterodimer configuration. The structure of a triethylene glycol linker was optimized to maximize binding interactions to the surface receptors on cells. The Cy5.5-labeled heterodimer QRH*–KSP*–E3–Cy5.5 demonstrated specific binding to each target and showed 3-fold greater fluorescence intensity and 2-fold higher affinity compared with those of either monomer alone. Peak uptake in xenograft tumors was observed at 2 h postinjection with systemic clearance by ∼24 h in vivo. Furthermore, ligand binding was evaluated on human esophageal specimens ex vivo, and 88% sensitivity and 87% specificity were found for the detection of either high-grade dysplasia (HGD) or EAC. This peptide heterodimer shows promise for targeted detection of early Barrett’s neoplasia in clinical study