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  1. Abstract

    Chimeric antigen receptor (CAR) monocyte and macrophage therapies are promising solid tumor immunotherapies that can overcome the challenges facing conventional CAR T cell therapy. mRNA lipid nanoparticles (mRNA‐LNPs) offer a viable platform for in situ engineering of CAR monocytes with transient and tunable CAR expression to reduce off‐tumor toxicity and streamline cell manufacturing. However, identifying LNPs with monocyte tropism and intracellular delivery potency is difficult using traditional screening techniques. Here, ionizable lipid design and high‐throughput in vivo screening are utilized to identify a new class of oxidized LNPs with innate tropism and mRNA delivery to monocytes. A library of oxidized (oLNPs) and unoxidized LNPs (uLNPs) is synthesized to evaluate mRNA delivery to immune cells. oLNPs demonstrate notable differences in morphology, ionization energy, and pKa, thereby enhancing delivery to human macrophages, but not T cells. Subsequently, in vivo library screening with DNA barcodes identifies an oLNP formulation, C14‐O2, with innate tropism to monocytes. In a proof‐of‐concept study, the C14‐O2 LNP is used to engineer functional CD19‐CAR monocytes in situ for robust B cell aplasia (45%) in healthy mice. This work highlights the utility of oxidized LNPs as a promising platform for engineering CAR macrophages/monocytes for solid tumor CAR monocyte therapy.

     
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  2. Abstract

    Resonant tunneling is a quantum‐mechanical effect in which electron transport is controlled by the discrete energy levels within a quantum‐well (QW) structure. A ferroelectric resonant tunneling diode (RTD) exploits the switchable electric polarization state of the QW barrier to tune the device resistance. Here, the discovery of robust room‐temperature ferroelectric‐modulated resonant tunneling and negative differential resistance (NDR) behaviors in all‐perovskite‐oxide BaTiO3/SrRuO3/BaTiO3QW structures is reported. The resonant current amplitude and voltage are tunable by the switchable polarization of the BaTiO3ferroelectric with the NDR ratio modulated by ≈3 orders of magnitude and an OFF/ON resistance ratio exceeding a factor of 2 × 104. The observed NDR effect is explained an energy bandgap between Ru‐t2gand Ru‐egorbitals driven by electron–electron correlations, as follows from density functional theory calculations. This study paves the way for ferroelectric‐based quantum‐tunneling devices in future oxide electronics.

     
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