Atomic-Level Matching Metal-Ion Organic Hybrid Interface to Enhance Energy Storage of Polymer-Based Composite Dielectrics.

In this work, a distinctive "metal-ion organic hybrid interface" (MOHI) between polyimide (PI) and calcium niobate (CNO) nanosheets is designed. The metal ions in the MOHI can achieve atomic-level matching not only with the inorganic CNO, but also with the PI chains, forming uniform and strong chemical bonds. These results are demonstrated by experiment and theory calculations. Significantly, the MOHI reduces the free volume and introduces deep traps across the filler-matrix interfacial area, thus suppressing the electric field distortion in PI-based composite dielectrics. Consequently, PI-based dielectric containing the MOHI exhibits excellent energy storage performance. The energy storage densities (Ue) of the composite dielectric reach 9.42 J cm-3 and 4.75 J cm-3 with energy storage efficiency (η) of 90% at 25 °C and 150 °C respectively, which are 2.6 and 11.6 times higher than those of pure PI. This study provides new ideas for polymer-based composite dielectrics in high energy storage.

Enhanced Lithium Storage Performance of α-MoO3/CNTs Composite Cathode.

Orthorhombic molybdenum oxide (α-MoO3), as a one-layered pseudocapacitive material, has attracted widespread attention due to its high theoretical lithium storage specific capacity (279 mAh/g) for lithium-ion batteries' cathode. Nevertheless, low conductivity, slack reaction kinetics, and large volume change during Li+ ions intercalation and deintercalation seriously limit the practical application of α-MoO3. Herein, we added a small number of CNTs (1.76%) to solve these problems in a one-step hydrothermal process for preparing the α-MoO3/CNTs composite. Because of the influence of CNTs, the α-MoO3 nanobelt in the α-MoO3/CNTs composite had a larger interlayer spacing, which provided more active sites and faster reaction kinetics for lithium storage. In addition, CNTs formed a three-dimensional conductive network between α-MoO3 nanobelts, enhanced the electrical conductivity of the composite, accelerated the electron conduction, shortened the ion transport path, and alleviated the structural fragmentation caused by the volume expansion during the α-MoO3 intercalation and deintercalation of Li+ ions. Therefore, the α-MoO3/CNTs composite cathode had a significantly higher rate performance and cycle life. After 150 cycles, the pure α-MoO3 cathode had almost no energy storage, but α-MoO3/CNTs composite cathode still retained 93 mAh/g specific capacity.

NKTR-255, a novel polymer-conjugated rhIL-15 with potent antitumor efficacy.

BACKGROUND: NKTR-255 is a novel polyethylene glycol-conjugate of recombinant human interleukin-15 (rhIL-15), which was designed to retain all known receptor binding interactions of the IL-15 molecule. We explored the biologic and pharmacologic differences between endogenous IL-15 receptor α (IL-15Rα)-dependent (NKTR-255 and rhIL-15) and IL-15Rα-independent (precomplexed rhIL-15/IL-15Rα) cytokines. METHODS: In vitro pharmacological properties of rhIL-15, NKTR-255 and precomplex cytokines (rhIL-15/IL-15Rα and rhIL-15 N72D/IL-15Rα Fc) were investigated in receptor binding, signaling and cell function. In vivo pharmacokinetic (PK) and pharmacodynamic profile of the cytokines were evaluated in normal mice. Finally, immunomodulatory effect and antitumor activity were assessed in a Daudi lymphoma model. RESULTS: NKTR-255 and rhIL-15 exhibited similar in vitro properties in receptor affinity, signaling and leukocyte degranulation, which collectively differed from precomplexed cytokines. Notably, NKTR-255 and rhIL-15 stimulated greater granzyme B secretion in human peripheral blood mononuclear cells versus precomplexed cytokines. In vivo, NKTR-255 exhibited a PK profile with reduced clearance and a longer half-life relative to rhIL-15 and demonstrated prolonged IL-15R engagement in lymphocytes compared with only transient engagement observed for rhIL-15 and precomplexed rhIL-15 N72D/IL-15Rα Fc. As a consequent, NKTR-255 provided a durable and sustained proliferation and activation of natural killer (NK) and CD8+ T cells. Importantly, NKTR-255 is more effective than the precomplexed cytokine at inducing functionally competent, cytotoxic NK cells in the tumor microenvironment and the properties of NKTR-255 translated into superior antitumor activity in a B-cell lymphoma model versus the precomplexed cytokine. CONCLUSIONS: Our results show that the novel immunotherapeutic, NKTR-255, retains the full spectrum of IL-15 biology, but with improved PK properties, over rhIL-15. These findings support the ongoing phase 1 first-in-human trial (NCT04136756) of NKTR-255 in participants with relapsed or refractory hematologic malignancies, potentially advancing rhIL-15-based immunotherapies for the treatment of cancer.

NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, and Marked Efficacy in Mouse Tumor Models.

PURPOSE: Aldesleukin, recombinant human IL2, is an effective immunotherapy for metastatic melanoma and renal cancer, with durable responses in approximately 10% of patients; however, severe side effects limit maximal dosing and thus the number of patients able to receive treatment and potential cure. NKTR-214 is a prodrug of conjugated IL2, retaining the same amino acid sequence as aldesleukin. The IL2 core is conjugated to 6 releasable polyethylene glycol (PEG) chains. In vivo, the PEG chains slowly release to generate active IL2 conjugates. EXPERIMENTAL DESIGN: We evaluated the bioactivity and receptor binding of NKTR-214 and its active IL2 conjugates in vitro; the tumor immunology, tumor pharmacokinetics, and efficacy of NKTR-214 as a single agent and in combination with anti-CTLA-4 antibody in murine tumor models. Tolerability was evaluated in non-human primates. RESULTS: In a murine melanoma tumor model, the ratio of tumor-killing CD8(+) T cells to Foxp3(+) regulatory T cells was greater than 400 for NKTR-214 compared with 18 for aldesleukin, supporting preferential activation of the IL2 receptor beta over IL2 receptor alpha, due to the location of PEG molecules. NKTR-214 provides a 500-fold greater exposure of the tumor to conjugated IL2 compared with aldesleukin. NKTR-214 showed efficacy as a single agent and provided durable immunity that was resistant to tumor rechallenge in combination with anti-CTLA-4 antibody. NKTR-214 was well tolerated in non-human primates. CONCLUSIONS: These data support further evaluation of NKTR-214 in humans for a variety of tumor types, adding to the repertoire of potent and potentially curative cancer immunotherapies.