Publications
358 results found
Kang DD, Hou X, Wang L, et al., 2024, Engineering LNPs with polysarcosine lipids for mRNA delivery, Bioactive Materials, Vol: 37, Pages: 86-93, ISSN: 2452-199X
Since the approval of the lipid nanoparticles (LNP)-mRNA vaccines against the SARS-CoV-2 virus, there has been an increased interest in the delivery of mRNA through LNPs. However, current LNP formulations contain PEG lipids, which can stimulate the generation of anti-PEG antibodies. The presence of these antibodies can potentially cause adverse reactions and reduce therapeutic efficacy after administration. Given the widespread deployment of the COVID-19 vaccines, the increased exposure to PEG may necessitate the evaluation of alternative LNP formulations without PEG components. In this study, we investigated a series of polysarcosine (pSar) lipids as alternatives to the PEG lipids to determine whether pSar lipids could still provide the functionality of the PEG lipids in the ALC-0315 and SM-102 LNP systems. We found that complete replacement of the PEG lipid with a pSar lipid can increase or maintain mRNA delivery efficiency and exhibit similar safety profiles in vivo.
May BJ, Hettiaratchy EC, Wang B, et al., 2024, Efficiency Limits in Coalesced AlGaN Nanowire Ultraviolet LEDs, Physica Status Solidi - Rapid Research Letters, Vol: 18, ISSN: 1862-6254
Nanowire AlGaN III-nitride LEDs are claimed as potential high-efficiency solid-state photon sources spanning to the short-wavelength deep ultraviolet (UV). Nanowire LEDs (NWLEDs) emitting in the UV are compared with a transparent n-AlGaN top electrode formed by coalescing the top region of nanowire–ensemble LEDs with commonly employed opaque conformal metallic electrodes used for nanowire-based devices. The use of a transparent contact results in an increase in the wall plug efficiency of >25×, exceeding the expected increase due to enhanced photon-extraction efficiency. Increased nanowire connectivity reduces the short-circuit pathways, enabling higher device yields of relatively large-area (>1 mm2) UV nanowire–ensemble LEDs. Despite these large relative improvements, the absolute output efficiency remains miniscule (<1 m%). Electroluminescence microscopy demonstrates that <0.1% of nanowires within the ensemble contribute to emission. The single-nanowire efficiency is estimated and points toward improvement of the homogeneity of the injection current as a crucial step for realizing commercially viable UV NWLEDs.
Xue Y, Zhang Y, Zhong Y, et al., 2024, LNP-RNA-engineered adipose stem cells for accelerated diabetic wound healing., Nat Commun, Vol: 15
Adipose stem cells (ASCs) have attracted considerable attention as potential therapeutic agents due to their ability to promote tissue regeneration. However, their limited tissue repair capability has posed a challenge in achieving optimal therapeutic outcomes. Herein, we conceive a series of lipid nanoparticles to reprogram ASCs with durable protein secretion capacity for enhanced tissue engineering and regeneration. In vitro studies identify that the isomannide-derived lipid nanoparticles (DIM1T LNP) efficiently deliver RNAs to ASCs. Co-delivery of self-amplifying RNA (saRNA) and E3 mRNA complex (the combination of saRNA and E3 mRNA is named SEC) using DIM1T LNP modulates host immune responses against saRNAs and facilitates the durable production of proteins of interest in ASCs. The DIM1T LNP-SEC engineered ASCs (DS-ASCs) prolong expression of hepatocyte growth factor (HGF) and C-X-C motif chemokine ligand 12 (CXCL12), which show superior wound healing efficacy over their wild-type and DIM1T LNP-mRNA counterparts in the diabetic cutaneous wound model. Overall, this work suggests LNPs as an effective platform to engineer ASCs with enhanced protein generation ability, expediting the development of ASCs-based cell therapies.
Boldrin D, Mihai AP, Zou B, et al., 2024, Correction to "Giant piezomagnetism in Mn3NiN", ACS Applied Materials and Interfaces, Vol: 16, Pages: 2997-2997, ISSN: 1944-8244
Berkbigler G, Liu Q, Hoefer N, et al., 2024, C<inf>2</inf>H<inf>2</inf>/CO<inf>2</inf> Separation with a Chain-Type Zn Pyrazolate MOF, European Journal of Inorganic Chemistry, Vol: 27, ISSN: 1434-1948
A novel Zn dipyrazolate metal-organic framework (MOF), Zn(azbpz) (azbpz2−=4,4′-azobis(3,5-dimethylpyrazolate), has been synthesized and structurally characterized using micro-crystal electron diffraction. The framework contains chain-type secondary building units comprised of tetrahedral Zn2+ ions bridged by pyrazolate groups, resulting in guest-accessible channels lined with methyl and azo functional groups. CO2, C2H2, C2H4, C2H6, C3H6, and C3H8 gas adsorption isotherms were measured to investigate the potential of Zn(azbpz) as an adsorbent for selective separation of binary gas mixtures. The data reveal selective adsorption of acetylene over CO2, and column breakthrough experiments demonstrate good performance for C2H2/CO2 separation.
Williams AJ, Reifsnyder A, Yu B, et al., 2023, Single crystal synthesis and properties of the two-dimensional van der Waals frustrated magnets, Mn<inf>2</inf>In<inf>2</inf>Se<inf>5</inf> and Mn<inf>2</inf>Ga<inf>2</inf>S<inf>5</inf>, Journal of Materials Chemistry C, Vol: 12, Pages: 1753-1762, ISSN: 2050-7526
There has been considerable interest in the search and design of two-dimensional (2D) van der Waals (vdW) compounds with exotic magnetic behavior. Here we establish the growth of phase pure crystals of Mn2In2Se5 and Mn2Ga2S5 and evaluate their structural, physical, and magnetic properties. These 2D vdW phases consist of double-octahedral thick Mn(S/Se)6 layers capped by InSe4 or GaS4 tetrahedra. Transmission electron microscopy confirms phase purity with the absence of impurity intergrowths of other closely related 2D vdW phases including Mn(In/Ga)2(Se/S)4 or In4Se3. Optical absorption measurements indicate these compounds have indirect band gaps of 1.33 and 1.58 eV, respectively. We also establish the Raman signatures for both compounds. Mn2In2Se5 and Mn2Ga2S5 are significantly frustrated magnetic materials due to the competing magnetic interactions in this double-thick triangular arrangement of metal atoms. They have magnetic transition temperatures of 7 and 13 K, respectively, compared to Weiss constants of −198 and −340 K, respectively. AC susceptibility experiments indicate that both Mn2In2Se5 and Mn2Ga2S5 exhibit significant spin glass character. The significant magnetic frustration makes these materials unique 2D magnetic vdW building blocks.
Pavlović RZ, Finnegan TJ, Metlushko A, et al., 2023, Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems., Chemistry, Vol: 29
We describe the preparation, dynamic, assembly characteristics of vase-shaped basket 13- along with its ability to form an inclusion complex with anticancer drug mitoxantrone in abiotic and biotic systems. This novel cavitand has a deep nonpolar pocket consisting of three naphthalimide sides fused to a bicyclic platform at the bottom while carrying polar glycines at the top. The results of 1 H Nuclear Magnetic Resonance (NMR), 1 H NMR Chemical Exchange Saturation Transfer (CEST), Calorimetry, Hybrid Replica Exchange Molecular Dynamics (REMD), and Microcrystal Electron Diffraction (MicroED) measurements are in line with 1 forming dimer [12 ]6- , to be in equilibrium with monomers 1(R) 3- (relaxed) and 1(S) 3- (squeezed). Through simultaneous line-shape analysis of 1 H NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket 1(R) 3- includes anticancer drug mitoxantrone (MTO2+ ) in its pocket to give stable binary complex [MTO⊂1]- (Kd =2.1 μM) that can be precipitated in vitro with UV light or pH as stimuli. Both in vitro and in vivo studies showed that the basket is nontoxic, while at a higher proportion with respect to MTO it reduced its cytotoxicity in vitro. With well-characterized internal dynamics and dimerization, the ability to include mitoxantrone, and biocompatibility, the stage is set to develop sequestering agents from deep-cavity baskets.
Liu T, Selcu CM, Wang B, et al., 2023, An atomically tailored chiral magnet with small skyrmions at room temperature, Communications Physics, Vol: 6
Creating materials that do not exist in nature can lead to breakthroughs in science and technology. Magnetic skyrmions are topological excitations that have attracted great attention recently for their potential applications in low power, ultrahigh density memory. A major challenge has been to find materials that meet the dual requirement of small skyrmions stable at room temperature. Here we meet both these goals by developing epitaxial FeGe films with excess Fe using atomic layer molecular beam epitaxy (MBE) far from thermal equilibrium. Our atomic layer design permits the incorporation of 20% excess Fe while maintaining a non-centrosymmetric crystal structure supported by theoretical calculations and necessary for stabilizing skyrmions. We show that the Curie temperature is well above room temperature, and that the skyrmions have sizes down to 15 nm as imaged by Lorentz transmission electron microscopy (LTEM) and magnetic force microscopy (MFM). The presence of skyrmions coincides with a topological Hall effect-like resistivity. These atomically tailored materials hold promise for future ultrahigh density magnetic memory applications.
Cheng S, Bagués N, Selcu CM, et al., 2023, Room-temperature magnetic skyrmions in Pt/Co/Cu multilayers, Physical Review B, Vol: 108, ISSN: 2469-9950
Magnetic skyrmions are promising for next-generation information storage and processing owing to their potential advantages in data storage density, robustness, and energy efficiency. The magnetic multilayers consisting of Pt, Co, and a third metal element X provide an ideal platform to study skyrmions due to their highly tunable magnetic properties. Here, we report the observation of room-temperature bubblelike Néel skyrmions in epitaxial Pt/Co/Cu multilayers in samples with multidomain states in zero field. The magneto-optic Kerr effect and a superconducting quantum interference device magnetometry are applied to investigate the shapes of the hysteresis loops, the magnetic anisotropy, and the saturation magnetization. By tuning the Co thickness and the number of periods, we achieve perpendicular and in-plane magnetized states and multidomain states that are identified by a wasp-waisted hysteresis loop. Skyrmions are directly imaged by magnetic force microscopy and Lorentz transmission electron microscopy. The development of room-temperature skyrmions in Pt/Co/Cu multilayers may lead to advances in skyrmion-related research and applications.
Zhang Y, Hou X, Du S, et al., 2023, Close the cancer-immunity cycle by integrating lipid nanoparticle-mRNA formulations and dendritic cell therapy., Nat Nanotechnol, Vol: 18, Pages: 1364-1374
Effective cancer immunotherapy is usually blocked by immunosuppressive factors in the tumour microenvironment, resulting in tumour promotion, metastasis and recurrence. Here we combine lipid nanoparticle-mRNA formulations and dendritic cell therapy (named CATCH) to boost the cancer-immunity cycle via progressive steps to overcome the immunosuppressive tumour microenvironment. Multiple types of sugar-alcohol-derived lipid nanoparticles are conceived to modulate the cancer-immunity cycle. First, one type of lipid nanoparticle containing CD40 ligand mRNA induces robust immunogenic cell death in tumoural tissues, leading to the release of tumour-associated antigens and the expression of CD40 ligand. Next, dendritic cells engineered by another type of lipid nanoparticle encapsulating CD40 mRNA are adoptively transferred, which are then activated by the CD40 ligand molecules in tumoural tissues. This promotes the secretion of multiple cytokines and chemokines, and the upregulation of co-stimulatory molecules on dendritic cells, which are crucial for reprogramming the tumour microenvironment and priming the T-cell responses. After dendritic cells present tumour-associated antigens to T cells, all the above stepwise events contribute to boosting a potent tumour-specific T-cell immunity that eradicates established tumours, suppresses distal lesions and prevents tumour rechallenge.
Duarte-Sanmiguel S, Salazar-Puerta AI, Panic A, et al., 2023, ICAM-1-decorated extracellular vesicles loaded with miR-146a and Glut1 drive immunomodulation and hinder tumor progression in a murine model of breast cancer., Biomater Sci, Vol: 11, Pages: 6834-6847
Tumor-associated immune cells play a crucial role in cancer progression. Myeloid-derived suppressor cells (MDSCs), for example, are immature innate immune cells that infiltrate the tumor to exert immunosuppressive activity and protect cancer cells from the host's immune system and/or cancer-specific immunotherapies. While tumor-associated immune cells have emerged as a promising therapeutic target, efforts to counter immunosuppression within the tumor niche have been hampered by the lack of approaches that selectively target the immune cell compartment of the tumor, to effectively eliminate "tumor-protecting" immune cells and/or drive an "anti-tumor" phenotype. Here we report on a novel nanotechnology-based approach to target tumor-associated immune cells and promote "anti-tumor" responses in a murine model of breast cancer. Engineered extracellular vesicles (EVs) decorated with ICAM-1 ligands and loaded with miR-146a and Glut1, were biosynthesized (in vitro or in vivo) and administered to tumor-bearing mice once a week for up to 5 weeks. The impact of this treatment modality on the immune cell compartment and tumor progression was evaluated via RT-qPCR, flow cytometry, and histology. Our results indicate that weekly administration of the engineered EVs (i.e., ICAM-1-decorated and loaded with miR-146a and Glut1) hampered tumor progression compared to ICAM-1-decorated EVs with no cargo. Flow cytometry analyses of the tumors indicated a shift in the phenotype of the immune cell population toward a more pro-inflammatory state, which appeared to have facilitated the infiltration of tumor-targeting T cells, and was associated with a reduction in tumor size and decreased metastatic burden. Altogether, our results indicate that ICAM-1-decorated EVs could be a powerful platform nanotechnology for the deployment of immune cell-targeting therapies to solid tumors.
Ortega-Pineda L, Rincon-Benavides MA, Cuellar-Gaviria TZ, et al., 2023, Engineered Extracellular Vesicles from Human Skin Cells Induce Pro-β-Cell Conversions in Pancreatic Ductal Cells, Advanced NanoBiomed Research, Vol: 3
Direct nuclear reprogramming has the potential to enable the development of β cell replacement therapies for diabetes that do not require the use of progenitor/stem cell populations. However, despite their promise, current approaches to β cell-directed reprogramming rely heavily on the use of viral vectors. Herein, the use of extracellular vesicles (EVs) derived from human dermal fibroblasts (HDFs) is explored as novel nonviral carriers of endocrine cell-patterning transcription factors, to transfect and transdifferentiate pancreatic ductal epithelial cells (PDCs) into hormone-expressing cells. Electrotransfection of HDFs with expression plasmids for Pdx1, Ngn3, and MafA (PNM) leads to the release of EVs loaded with PNM at the gene, mRNA, and protein levels. Exposing PDC cultures to PNM-loaded EVs leads to successful transfection and increases PNM expression in PDCs, which ultimately result in endocrine cell-directed conversions based on the expression of insulin/c-peptide, glucagon, and glucose transporter 2 (Glut2). These findings are further corroborated in vivo in a mouse model following intraductal injection of PNM- versus sham-loaded EVs. Collectively, these findings suggest that dermal fibroblast-derived EVs can potentially serve as a powerful platform technology for the development and deployment of nonviral reprogramming-based cell therapies for insulin-dependent diabetes.
Cheng S, Nrisimhamurty M, Zhou T, et al., 2023, Epitaxial Kagome Thin Films as a Platform for Topological Flat Bands., Nano Lett, Vol: 23, Pages: 7107-7113
Systems with flat bands are ideal for studying strongly correlated electronic states and related phenomena. Among them, kagome-structured metals such as CoSn have been recognized as promising candidates due to the proximity between the flat bands and the Fermi level. A key next step will be to realize epitaxial kagome thin films with flat bands to enable tuning of the flat bands across the Fermi level via electrostatic gating or strain. Here, we report the band structures of epitaxial CoSn thin films grown directly on the insulating substrates. Flat bands are observed by using synchrotron-based angle-resolved photoemission spectroscopy (ARPES). The band structure is consistent with density functional theory (DFT) calculations, and the transport properties are quantitatively explained by the band structure and semiclassical transport theory. Our work paves the way to realize flat band-induced phenomena through fine-tuning of flat bands in kagome materials.
Feng X, Liu Y, Kamensky D, et al., 2023, Functional mechanical behavior of the murine pulmonary heart valve., Sci Rep, Vol: 13
Genetically modified mouse models provide a versatile and efficient platform to extend our understanding of the underlying disease processes and evaluate potential treatments for congenital heart valve diseases. However, applications have been limited to the gene and molecular levels due to the small size of murine heart valves, which prohibits the use of standard mechanical evaluation and in vivo imaging methods. We have developed an integrated imaging/computational mechanics approach to evaluate, for the first time, the functional mechanical behavior of the murine pulmonary heart valve (mPV). We utilized extant mPV high resolution µCT images of 1-year-old healthy C57BL/6J mice, with mPVs loaded to 0, 10, 20 or 30 mmHg then chemically fixed to preserve their shape. Individual mPV leaflets and annular boundaries were segmented and key geometric quantities of interest defined and quantified. The resulting observed inter-valve variations were small and consistent at each TVP level. This allowed us to develop a high fidelity NURBS-based geometric model. From the resultant individual mPV geometries, we developed a mPV shape-evolving geometric model (SEGM) that accurately represented mPV shape changes as a continuous function of transvalvular pressure. The SEGM was then integrated into an isogeometric finite element based inverse model that estimated the individual leaflet and regional mPV mechanical behaviors. We demonstrated that the mPV leaflet mechanical behaviors were highly anisotropic and nonlinear, with substantial leaflet and regional variations. We also observed the presence of strong axial mechanical coupling, suggesting the important role of the underlying collagen fiber architecture in the mPV. When compared to larger mammalian species, the mPV exhibited substantially different mechanical behaviors. Thus, while qualitatively similar, the mPV exhibited important functional differences that will need to accounted for in murine heart valve studies. T
Salazar-Puerta AI, Kordowski M, Cuellar-Gaviria TZ, et al., 2023, Engineered Extracellular Vesicle-Based Therapies for Valvular Heart Disease, Cellular and Molecular Bioengineering, Vol: 16, Pages: 309-324, ISSN: 1865-5025
Introduction: Valvular heart disease represents a significant burden to the healthcare system, with approximately 5 million cases diagnosed annually in the US. Among these cases, calcific aortic stenosis (CAS) stands out as the most prevalent form of valvular heart disease in the aging population. CAS is characterized by the progressive calcification of the aortic valve leaflets, leading to valve stiffening. While aortic valve replacement is the standard of care for CAS patients, the long-term durability of prosthetic devices is poor, calling for innovative strategies to halt or reverse disease progression. Here, we explor the potential use of novel extracellular vesicle (EV)-based nanocarriers for delivering molecular payloads to the affected valve tissue. This approach aims to reduce inflammation and potentially promote resorption of the calcified tissue. Methods: Engineered EVs loaded with the reprogramming myeloid transcription factors, CEBPA and Spi1, known to mediate the transdifferentiation of committed endothelial cells into macrophages. We evaluated the ability of these engineered EVs to deliver DNA and transcripts encoding CEBPA and Spil into calcified aortic valve tissue obtained from patients undergoing valve replacement due to aortic stenosis. We also investigated whether these EVs could induce the transdifferentiation of endothelial cells into macrophage-like cells. Results: Engineered EVs loaded with CEBPA + Spi1 were successfully derived from human dermal fibroblasts. Peak EV loading was found to be at 4 h after nanotransfection of donor cells. These CEBPA + Spi1 loaded EVs effectively transfected aortic valve cells, resulting in the successful induction of transdifferentiation, both in vitro with endothelial cells and ex vivo with valvular endothelial cells, leading to the development of anti-inflammatory macrophage-like cells. Conclusions: Our findings highlig
Reifsnyder A, Nawwar M, Hachtel J, et al., 2023, Vibrational Spectroscopy of MnPSe3 in the Scanning Transmission Electron Microscope., Microsc Microanal, Vol: 29, Pages: 647-648
Hsu Y-H, Hassan A, Trout A, et al., 2023, The Characterization of Hydroxyapatite and Octa-calcium Phosphate with Electron Energy Loss Spectroscopy., Microsc Microanal, Vol: 29, Pages: 1223-1225
Reifsnyder A, Lupini AR, Hachtel J, et al., 2023, Development of a Low-Cost, Modular Cryo-Transfer Station for the Side-Entry Transmission Electron Microscope., Microsc Microanal, Vol: 29
Trout AH, Hassan A, Koerner H, et al., 2023, Unraveling the Covalency of the Ti Oxidation State in Ti3C2Tx via Electron Energy-loss Spectroscopy., Microsc Microanal, Vol: 29, Pages: 1801-1802
Ford BR, McComb DW, 2023, Exploring Electron Energy-loss Spectroscopy for the Characterization and Mapping of Structured Fluids., Microsc Microanal, Vol: 29, Pages: 1774-1776
Salazar-Puerta AI, Rincon-Benavides MA, Cuellar-Gaviria TZ, et al., 2023, Engineered Extracellular Vesicles Derived from Dermal Fibroblasts Attenuate Inflammation in a Murine Model of Acute Lung Injury., Adv Mater, Vol: 35
Acute respiratory distress syndrome (ARDS) represents a significant burden to the healthcare system, with ≈200 000 cases diagnosed annually in the USA. ARDS patients suffer from severe refractory hypoxemia, alveolar-capillary barrier dysfunction, impaired surfactant function, and abnormal upregulation of inflammatory pathways that lead to intensive care unit admission, prolonged hospitalization, and increased disability-adjusted life years. Currently, there is no cure or FDA-approved therapy for ARDS. This work describes the implementation of engineered extracellular vesicle (eEV)-based nanocarriers for targeted nonviral delivery of anti-inflammatory payloads to the inflamed/injured lung. The results show the ability of surfactant protein A (SPA)-functionalized IL-4- and IL-10-loaded eEVs to promote intrapulmonary retention and reduce inflammation, both in vitro and in vivo. Significant attenuation is observed in tissue damage, proinflammatory cytokine secretion, macrophage activation, influx of protein-rich fluid, and neutrophil infiltration into the alveolar space as early as 6 h post-eEVs treatment. Additionally, metabolomics analyses show that eEV treatment causes significant changes in the metabolic profile of inflamed lungs, driving the secretion of key anti-inflammatory metabolites. Altogether, these results establish the potential of eEVs derived from dermal fibroblasts to reduce inflammation, tissue damage, and the prevalence/progression of injury during ARDS via nonviral delivery of anti-inflammatory genes/transcripts.
Irvine CT, Hoefer N, Moser MJ, et al., 2023, Diselenide Dianion’s Dual Powers: PdSe<inf>2</inf> Polymorph Control and Pd<inf>3</inf>Se<inf>10</inf> Superatomic Crystal Creation, Chemistry of Materials, Vol: 35, Pages: 4404-4411, ISSN: 0897-4756
There is a diverse family of palladium selenide compounds, including semiconducting orthorhombic PdSe2 (O-PdSe2) and monoclinic PdSe2 (M-PdSe2), which are unusual among transition-metal dichalcogenides as they are composed of diselenide dianions Se22-. Thus far, the solution syntheses of materials with Se-Se bonds typically require the in situ reduction of Se precursors. Here, we explore the use of electrochemically precise reactions between Na2Se2 and a Pd2+ source, Na2PdCl4, as a solution-phase route to selectively form different PdSe2 polymorphs in the absence of surfactants. By altering the reactant molar ratios and time, we map out a synthetic phase space diagram that shows how to create a wide variety of palladium selenide phases. With increasing Se22-/Pd2+ molar ratios, regions are identified where Pd17Se15, M-PdSe2, and O-PdSe2 exist as the dominant or exclusive thermodynamic product. Additionally, we discover Pd3Se10, a superatomic crystal composed of Pd6Se20 cube-shaped clusters held together by van der Waals forces, which forms as a kinetic product under short reaction times. In total, the use of the diselenide dianion precursor allows for the selective solution-phase synthesis of M-PdSe2 or O-PdSe2, as well as the discovery of a previously unreported palladium selenide phase.
Brennan MC, Veghte DP, Ford BR, et al., 2023, Photolysis of Mixed Halide Perovskite Nanocrystals, ACS Energy Letters, Vol: 8, Pages: 2150-2158
Colloidal mixed halide perovskite nanocrystals (NCs) irreversibly degrade when exposed to ultraviolet-visible irradiation. Here, mixed halide perovskite NC photolysis is tracked via mass spectrometry, electron microscopy, and photoluminescence. The data shows continuous wave ultraviolet-visible irradiation causes the heavier halides within the alloy to sublimate. This ultimately transforms CsPb(I1-xBrx)3 and CsPb(Cl1-xBrx)3 (x ≈ 0.50) NCs into CsPbBr3 and CsPbCl3 NCs, respectively. Time-resolved mass spectrometry demonstrates real-time desorption of volatile halide species (e.g., I2(g)/HI(g)) during irradiation. Energy-dispersive X-ray spectroscopy confirms near complete expulsion of I- from CsPb(I1-xBrx)3 and Br- from CsPb(Cl1-xBrx)3 NCs. Electron diffraction and cathodoluminescence establish lattice contractions and emission blueshifts consistent with formation of single halide perovskites from parent mixed halide alloys. Finally, increasing photolysis rates at higher temperatures follow an Arrhenius relationship with an effective activation energy of ∼62 kJ mol-1 for CsPb(I1-xBrx)3 NCs (x ≈ 0.50). Altogether, this work provides important insight into the photolysis of colloidal perovskite NC alloys.
Zhang Y, Yan J, Hou X, et al., 2023, STING Agonist-Derived LNP-mRNA Vaccine Enhances Protective Immunity Against SARS-CoV-2., Nano Lett, Vol: 23, Pages: 2593-2600
Lipid nanoparticle (LNP)-mediated delivery of messenger RNA (mRNA) COVID-19 vaccines has provided large-scale immune protection to the public. To elicit a robust immune response against SARS-CoV-2 infections, antigens produced by mRNAs encoding SARS-CoV-2 Spike glycoprotein need to be efficiently delivered and presented to antigen-presenting cells such as dendritic cells (DCs). As concurrent innate immune stimulation can facilitate the antigen presentation process, a library of non-nucleotide STING agonist-derived amino lipids (SALs) was synthesized and formulated into LNPs for mRNA delivery. SAL12 lipid nanoparticles (SAL12-LNPs) were identified as most potent in delivering mRNAs encoding the Spike glycoprotein (S) of SARS-CoV-2 while activating the STING pathway in DCs. Two doses of SAL12 S-LNPs by intramuscular immunization elicited potent neutralizing antibodies against SARS-CoV-2 in mice.
Colby R, Williams REA, Carpenter DL, et al., 2023, Identifying and imaging polymer functionality at high spatial resolution with core-loss EELS., Ultramicroscopy, Vol: 246
Electron energy loss spectroscopy (EELS) is a proven tool for probing materials chemistry at high spatial resolution. Core-loss EELS fine structure should allow measurement of local polymer chemistry. For organic materials, sensitivity to radiolysis is expected to limit the resolution achievable with EELS: but core-loss EELS has proven difficult at any resolution, yielding inconsistent spectra that compare unfavorably with theoretically analogous x-ray absorption spectra. Many of the previously identified shortcomings should not be limiting factors on modern equipment. This study establishes that EELS can generate identifiable carbon K-edge spectra for a range of common polymer types and chemistry, and demonstrates fine structure features matching prior x-ray absorption spectra. EELS fine structure features broaden intuitively with the instrument's energy resolution, and beam-induced features are readily differentiated by collecting spectra at a series of doses. The results are demonstrated with spectrum images of a model polymer blend, and used to estimate practical pixel sizes that can be used for mapping core-loss EELS as a function of electron dose.
Du S, Li W, Zhang Y, et al., 2023, Cholesterol-Amino-Phosphate (CAP) Derived Lipid Nanoparticles for Delivery of Self-Amplifying RNA and Restoration of Spermatogenesis in Infertile Mice., Adv Sci (Weinh), Vol: 10
Male infertility caused by genetic mutations is an important type of infertility. Currently, there is no reliable method in the clinic to address this medical need. The emergence of mRNA therapy provides a possible strategy for restoring mutant genes in the reproductive system. However, effective delivery of mRNA to spermatocytes remains a formidable challenge. Here a series of cholesterol-amino-phosphate (CAP) lipids are reported by integrating three bioactive moieties into a geometric structure, which is favorable for mRNA delivery. The results demonstrate that CAP-derived lipid nanoparticles (CAP LNPs) can deliver RNA including traditional mRNA and self-amplifying RNA (saRNA) encoding DNA Meiotic Recombinase 1 (Dmc1) protein in spermatocytes and treat male infertility caused by the Dmc1 gene mutation. Notably, the delivery efficiency of CAP LNPs is significantly higher than that of the MC3 and ALC-0315 LNPs, which is consistent with the design of CAP molecules. More importantly, a single injection of CAP LNPs-saRNA can produce Dmc1 protein for an extended period, which restores the spermatogenesis in the Dmc1 gene knockout mouse model. Overall, this study proves the concept of LNPs for the delivery of mRNA to spermatocytes, which provides a unique method to probe male infertility caused by the genetic mutation.
Rincon-Benavides MA, Mendonca NC, Cuellar-Gaviria TZ, et al., 2023, Engineered Vasculogenic Extracellular Vesicles Drive Nonviral Direct Conversions of Human Dermal Fibroblasts into Induced Endothelial Cells and Improve Wound Closure, Advanced Therapeutics, Vol: 6
Vasculogenic cell therapies have emerged as a powerful tool to increase vascularization and promote tissue repair/regeneration. Current approaches to cell therapies, however, rely mostly on progenitor cells, which pose significant risks (e.g., uncontrolled differentiation, tumorigenesis, and genetic/epigenetic abnormalities). Moreover, reprogramming methodologies used to generate induced endothelial cells (iECs) from induced pluripotent stem cells rely heavily on viral vectors, which pose additional translational limitations. This work describes the development of engineered human extracellular vesicles (EVs) capable of driving reprogramming-based vasculogenic therapies without the need for progenitor cells and/or viral vectors. EVs are derived from primary human dermal fibroblasts (HDFs), and are engineered to pack transcription factor genes/transcripts of ETV2, FLI1, and FOXC2 (EFF). In addition to EFF, the engineered EVs are also loaded with transcripts of angiogenic factors (e.g., VEGF-A, VEGF-KDR, FGF2). In vitro and in vivo studies indicate that such EVs effectively transfected HDFs and drive direct conversions towards iECs within 714 days. Finally, wound healing studies in mice indicate that engineered EVs lead to improved wound closure and vascularity. Altogether, these results show the potential of engineered human vasculogenic EVs to drive direct reprogramming processes of somatic cells towards iECs, and facilitate tissue repair/regeneration.
Wang B, McComb DW, 2023, Phase imaging in scanning transmission electron microscopy using bright-field balanced divergency method., Ultramicroscopy, Vol: 245
We introduce a phase imaging mechanism for scanning transmission electron microscopy that exploits the complementary intensity changes of transmitted disks at different scattering angles. For scanning transmission electron microscopy, this method provides a straightforward, dose-efficient, and noise-robust phase imaging, from atomic resolution to intermediate length scales, as a function of scattering angles and probe defocus. At atomic resolution, we demonstrate that the phase imaging using the method can detect both light and heavy atomic columns. Furthermore, we experimentally apply the method to the imaging of nanoscale magnetic phases in FeGe samples. Compared with conventional methods, phase retrieval using the new method has higher effective spatial resolution and robustness to non-phase background contrast. Our method complements traditional phase imaging modalities in electron microscopy and has the potential to be extended to other scanning transmission techniques and to characterize many emerging material systems.
Sternlicht H, McComb DW, Padture NP, 2022, Interaction of ytterbium pyrosilicate environmental-barrier-coating ceramics with molten calcia-magnesia-aluminosilicate glass: Part II, Interfaces, Acta Materialia, Vol: 241, ISSN: 1359-6454
Interfaces in as-processed β-Yb2Si2O7 environmental barrier coating (EBC) ceramics, and those after high-temperature (1500 °C) interaction with a calcia-magnesia-aluminosilicate (CMAS) glass from Part I are studied in further detail using high-resolution transmission electron microscopy (HRTEM), annular dark field scanning TEM (ADF STEM) and high-angle ADF (HAADF) STEM. Disconnections are detected, or inferred, at twin and general grain-boundaries and also at phase boundaries. Grain-boundary and facet planes are found to be aligned parallel to {110} planes of β-Yb2Si2O7. When detected, step planes are also found to be aligned parallel to β-Yb2Si2O7 {110} planes. At the same time, the dislocation component has major projections aligned parallel to {110} planes of β-Yb2Si2O7. As such, both the step and the dislocation components of the disconnections are anisotropic. The tendency of the grain-boundary and facet planes at interfaces in the system to align parallel to β-Yb2Si2O7{110} planes, both before and after CMAS-interaction, is discussed. The chemistry of grain-boundaries in the vicinity of the disconnections is found to be non-stoichiometric, but this by itself cannot account for the extended contrast variations along twin boundaries. Thus, contrast variations along grain boundaries are associated mainly with the presence of disconnections and associated strain, as well as long-range distortions in the unit cells in twin boundaries. These anisotropic disconnections are associated with the mechanisms of grain-boundary and phase-boundary migration, and thus, they have implications on the evolution of microstructures in this system. Combined insights from Part I and this Part II elucidate the nature of the interfaces in β-Yb2Si2O7 EBC ceramic and the mechanisms of CMAS glass penetration.
Hettiaratchy EC, Wang B, Dheenan A, et al., 2022, Quantitative x-ray diffraction analysis of strain and interdiffusion in β-Ga<inf>2</inf>O<inf>3</inf>superlattices of μ -Fe<inf>2</inf>O<inf>3</inf>and β-(Al<inf>x</inf>Ga<inf>1-x</inf>)<inf>2</inf>O<inf>3</inf>, Journal of Vacuum Science and Technology A: Vacuum, Surfaces and Films, Vol: 40, ISSN: 0734-2101
Superlattices composed of either monoclinic μ-Fe2O3 or β-(AlxGa1-x)2O3 with β-Ga2O3 spacers are grown on (010) β-Ga2O3 substrates using plasma-assisted molecular beam epitaxy. High-resolution x-ray diffraction data are quantitatively fit using commercial dynamical x-ray diffraction software (LEPTOS) to obtain layer thicknesses, strain, and compositions. The strain state of β-(AlxGa1-x)2O3 and μ-Fe2O3 superlattices as characterized using reciprocal space maps in the symmetric (020) and asymmetric (420) diffraction conditions indicates coherent growths that are strained to the (010) β-Ga2O3 lattice. β-(AlxGa1-x)2O3 and μ-Fe2O3 superlattices grown at hotter substrate temperatures result in crystal structures with better coherency and reduced defects compared to colder growths. The growth rate of μ-Fe2O3 is ∼2.6 nm/min at Tsub = 700 °C and drops to ∼1.6 nm/min at Tsub = 800 °C due to increased Fe interdiffusion at hotter substrate temperatures. Scanning transmission electron microscopy data of a μ-Fe2O3 superlattice grown at Tsub = 700 °C confirm that there is significant diffusion of Fe atoms into β-Ga2O3 layers.
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