A potential bivalent mRNA vaccine candidate protects against both RSV and SARS-CoV-2 infections.

As the world continues to confront severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV) is also causing severe respiratory illness in millions of infants, elderly individuals, and immunocompromised people globally. Exacerbating the situation is the fact that co-infection with multiple viruses is occurring, something which has greatly increased the clinical severity of the infections. Thus, our team developed a bivalent vaccine that delivered mRNAs encoding SARS-CoV-2 Omicron spike (S) and RSV fusion (F) proteins simultaneously, SF-LNP, which induced S and F protein-specific binding antibodies and cellular immune responses in BALB/c mice. Moreover, SF-LNP immunization effectively protected BALB/c mice from RSV infection and hamsters from SARS-CoV-2 Omicron infection. Notably, our study pointed out the antigenic competition problem of bivalent vaccines and provided a solution. Overall, our results demonstrated the potential of preventing two infectious diseases with a single vaccine and provided a paradigm for the subsequent design of multivalent vaccines.

Helper Lipid-Enhanced mRNA Delivery for Treating Metabolic Dysfunction-Associated Fatty Liver Disease.

Lipid nanoparticles (LNPs) represent the forefront of mRNA delivery platforms, yet achieving precise delivery to specific cells remains a challenge. The current targeting strategies complicate the formulation and impede the regulatory approval process. Here, through a straightforward regulation of helper lipids within LNPs, we introduce an engineered LNP designed for targeted delivery of mRNA into hepatocytes for metabolic dysfunction-associated fatty liver disease (MAFLD) treatment. The optimized LNP, supplied with POPC as the helper lipid, exhibits a 2.49-fold increase in mRNA transfection efficiency in hepatocytes compared to that of FDA-approved LNPs. CTP:phosphocholine cytidylyltransferase α mRNA is selected for delivery to hepatocytes through the optimized LNP system for self-calibration of phosphatidylcholine levels to prevent lipid droplet expansion in MAFLD. This strategy effectively regulates lipid homeostasis, while demonstrating proven biosafety. Our results present a mRNA therapy for MAFLD and open a new avenue for discovering potent lipids enabling mRNA delivery to specific cells.

Multicomponent Synthesis of Imidazole-Based Ionizable Lipids for Highly Efficient and Spleen-Selective Messenger RNA Delivery.

The spleen emerges as a pivotal target for mRNA delivery, prompting a continual quest for specialized and efficient lipid nanoparticles (LNPs) designed to enhance spleen-selective transfection efficiency. Here we report imidazole-containing ionizable lipids (IMILs) that demonstrate a pronounced preference for mRNA delivery into the spleen with exceptional transfection efficiency. We optimized IMIL structures by constructing and screening a multidimensional IMIL library containing multiple heads, tails, and linkers to perform a structure-activity correlation analysis. Following high-throughput in vivo screening, we identified A3B7C2 as a top-performing IMIL in spleen-specific mRNA delivery via the formulated LNPs, achieving a remarkable 98% proportion of splenic transfection. Moreover, A3B7C2-based LNPs are particularly potent in splenic dendritic cell transfection. Comparative analyses revealed that A3B7C2-based LNPs achieved a notable 2.8-fold and 12.9-fold increase in splenic mRNA transfection compared to SM102 and DLin-MC3-DMA lipid formulations, respectively. Additionally, our approach yielded an 18.3-fold enhancement in splenic mRNA expression compared to the SORT method without introducing additional anionic lipids. Collectively, these IMILs highlight promising avenues for further research in spleen-selective mRNA delivery. This work offers valuable insights for the swift discovery and rational design of ionizable lipid candidates tailored for spleen-selective transfection, thereby facilitating the application of mRNA therapeutics in spleen-related interventions.

Tuning Morphologies of Metal-Organic Framework-Derived Ni3P/Ni Carbon Nanocomposites for Water Oxidation.

The oxygen evolution reaction (OER) frequently acts as a kinetic bottleneck in various energy storage and conversion systems. Effective electrocatalysts for the OER play a crucial role in reducing the reaction barrier and expediting the reaction. Multicomponent transition metal phosphides (TMPs) have garnered an extensive amount of attention as a result of their exceptional performance in the OER. Here, we present a direct method for preparing two intrinsic morphologies of metal-organic frameworks (MOFs), barrel-like BMM-10 and pancake-like BMM-10(Ac), achieved by establishing a protonation/deprotonation equilibrium with varying NO3-/Ac- ratios. The BMM-10(Ac)-C catalyst was synthesized via heat treatment of the BMM-10(Ac) precursor, exhibiting superior OER performance. It realized an overpotential of 286 mV at a current density of 10 mA cm-2, with a Tafel slope of 111.17 mV decade-1 and a current retention of 98.03%. This improvement arises from the synergistic interaction between Ni3P/Ni nanoparticles and the partially graphitic carbon layer, augmenting the exposure of active sites. Furthermore, alterations in the morphological features of MOF-derived Ni3P/Ni carbon nanocomposites adjusted the active electrochemical surface area, thereby modulating the overall OER performance of the corresponding TMP carbon nanocomposites. This methodology can be extended to control the morphology of other MOFs and their derivatives, providing innovative avenues for the design and synthesis of new MOF-based TMP nanomaterials.

In-based coordination polymer-derived carbon nanoribbons with abundant CoP nanoparticles in carbon nanotubes for water oxidation.

The sluggish oxygen evolution reaction (OER) in overall electrocatalytic water splitting poses a significant challenge in hydrogen production. A series of transition metal phosphides are emerging as promising electrocatalysts, effectively modulating the charge distribution of surrounding atoms for OER. In this study, a highly efficient OER electrocatalyst (CoP-CNR-CNT) was successfully synthesized through the pyrolysis and phosphatization of a Co-doped In-based coordination polymer, specifically InOF-25. This process resulted in evenly dispersed CoP nanoparticles encapsulated in coordination polymer-derived carbon nanoribbons. The synthesized CoP-CNR-CNT demonstrated a competitive OER activity with a smaller overpotential (η10) of 295.7 mV at 10 mA cm-2 and a satisfactory long-term stability compared to the state-of-the-art RuO2 (η10 = 353.7 mV). The high OER activity and stability can be attributed to the high conductivity of the carbon network, the abundance of CoP particles, and the intricate nanostructure of nanoribbons/nanotubes. This work provides valuable insights into the rational design and facile preparation of efficient non-precious metal-based OER electrocatalysts from inorganic-organic coordination polymers, with potential applications in various energy conversion and storage systems.

Highly thermostable RhB@Zr-Eddc for the selective sensing of nitrofurazone and efficient white light emitting diode.

Highly thermostable RhB@Zr-Eddc composites with the Rhodamine B (RhB) enclosed into the nanocages of Zr-Eddc was synthesized by one-pot method under hydrothermal conditions, whose structure, morphology and stability were characterized through the X-ray powder diffractometry (XRD), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). RhB@Zr-Eddc showed the highly thermal stability up to 550°C and emitted the bright red-light emission at 605 nm, which could highly selective detect the nitrofurazone (NFZ) among eleven other antibiotics in aqueous solution. Furthermore, via combining the RhB@Zr-Eddc with commercial green phosphor (Y3Al5O12:Ce3+, Ga3+), the mixture was encapsulated onto a 455 nm blue LED chip, creating an ex-cellent white light emitting diode (WLED) device with the correlated colour temperature (CCT) of 4710 K, luminous efficiency (LE) of 43.17 lm/w and Color Rendering Index (CRI) of 89.2.

The N-anchoring effect in NH2-functionalized MOF-derived iron-carbon nanomaterials for oxygen reduction.

The incorporation of an iron source into NH2-MOF-5, followed by thermal decomposition, yields a porous metal-carbon catalyst (MOF5A-Fe@NC). This catalyst possesses significant N content, a high degree of graphitization, and abundant Fe-Nx sites, which contribute to enhanced oxygen reduction. Specifically, the obtained MOF5A-Fe@NC demonstrates a positive onset potential (0.972 V), a substantial limiting current density (4.815 mA cm-2), and a small Tafel slope (58.7 mV dec-1), and maintains a high current retention of 96.3% after 10 hours.

Heterogeneous-Structure-Based AuNBs@TiO2 Nano-Photosensitizers for Computed Tomography Imaging Guided NIR-II Photodynamic Therapy and Cancer Metastatic Prevention.

Photodynamic therapy (PDT) is a minimally invasive cancer treatment that, despite its significant attention, faces limitations in penetration depth, which restrict its effectiveness. Herein, it is found that gold nanobipyramid (AuNBs) coated with TiO2 can form a core-shell heterogeneous structure (AuNBs@TiO2) with strong absorption at second near infrared (NIR-II) region. A substantial quantity of reactive oxygen species (ROS), including singlet oxygen (1O2), superoxide anion radicals, and hydroxyl radicals, can be rapidly generated when subjecting the AuNBs@TiO2 aqueous suspension to 1064 nm laser irradiation. The quantum yield for sensitization of 1O2 by AuNBs@TiO2 is 0.36 at 1064 nm light excitation. In addition, the Au element as high-Z atoms in the nanosystem can improve the ability of computed tomographic (CT) imaging. As compared to commercial iohexol, the AuNBs@TiO2 nanoparticle exhibits significantly better CT imaging effect, which can be used to guide PDT. In addition, the nano-photosensitizer shows a remarkable therapeutic effect against established solid tumors and prevents tumor metastasis and potentiates immune checkpoint blockade therapy. More importantly, here the great potentials of AuNBs@TiO2 are highlighted as a theranostic platform for CT-guided cancer photodynamic immunotherapy.

Targeting Decidual CD16+ Immune Cells with Exosome-Based Glucocorticoid Nanoparticles for Miscarriage.

Immune dysfunction in early pregnancy including overactivation of cytotoxic CD16+ NK cells and proinflammatory M1 macrophages at the maternal-fetal interface interferes with trophoblast invasion, spiral artery remodeling, and decidualization, potentially leading to miscarriage. Immunosuppressants like glucocorticoids (GCs) are used to regulate the immune microenvironment in clinical treatment, but the lack of safe and efficient tissue-specific drug delivery systems, especially immune cell-specific vectors, limits their widespread clinical application. Here, a previously uncharacterized delivery system is reported, termed GC-Exo-CD16Ab, in which GCs are loaded into purified exosomes derived from human umbilical cord mesenchymal stem cells, and subsequently decorated with antibody CD16Ab. GC-Exo-CD16Ab is biocompatible and has remarkable delivery efficiency toward CD16+ decidual natural killer (NK) cells and CD16+ macrophages in mice. This innovative approach effectively suppresses the cytotoxicity of decidual NK cells, inhibits M1 macrophage polarization, and regulates the decidual microenvironment, thereby enhancing placental and fetal morphology, and ultimately mitigating miscarriage risk in the abortion-prone mice. The developed GC-Exo-CD16Ab provides a feasible platform for precise and tissue-specific therapeutic strategies for miscarriage and pregnancy-related diseases.

An mpox quadrivalent mRNA vaccine protects mice from lethal vaccinia virus challenge.

The outbreak of 2022 monkeypox virus (MPXV) infection in nonendemic regions is a global public health concern. A highly effective and safe MPXV vaccine that is available to the general public is urgently needed to control the mpox pandemic. Here, we developed a multivalent mRNA vaccine candidate, MPXV-1103, which expresses the full-length B6, A35, A29 and M1 proteins with three flexible linkers (G4S1)3 in a single sequence. Compared with the monovalent MPXV mRNA vaccine candidates or the quadrivalent mRNA vaccine from mixtures of the four monovalent MPXV mRNA vaccines, MPXV-1103 elicits a robust humoral response and an MPXV-specific T-cell response and protects mice from lethal vaccinia virus (VACV) challenge, with no live virus detected in the nasal or lungs even at dosages as low as 1 µg. Furthermore, analysis of complete blood counts and photomicrographs of tissue from the main organs of mice vaccinated with MPXV-1103 at doses of 5 µg and 20 µg revealed that two doses of MPXV-1103 did not cause any observable pathological changes in the mice. Collectively, our results suggest that MPXV-1103, with features of high efficacy, safety and a simplified manufacturing process, is a promising vaccine candidate for defending against MPXV infection.

Long-term immune response to Omicron-specific mRNA vaccination in mice, hamsters, and nonhuman primates.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron and its subvariants (such as BQ.1, XBB and the latest variants, including XBB.1.16, EG.5, and BA.2.86), as the dominant variants, currently account for almost all new infections in the world due to their high transmissibility and immune escape ability. Omicron-specific mRNA vaccines showed great potential to protect against Omicron infections. However, whether the vaccine could provide long-term protection is unknown. Toward this goal, we evaluated the immunogenicity of a preclinical Omicron (BA.1)-specific mRNA vaccine (SOmicron-6P) in different animal models. SOmicron-6P induced the highest levels of antibody titers at 1-2 weeks in different animals after the second dose. Even 9 months after the immunization, we observed modest neutralizing activity against Omicron subvariants in macaques. In addition, immunological memory cells can be rapidly reactivated upon stimulation. SOmicron-6P at concentrations higher than 10 µg effectively protected hamsters from BA.1 challenge 253 days after the first immunization, which could be attributed to the reactivation of immune systems. In addition, the toxicity tests conducted in rats revealed a highly favorable biosafety profile for SOmicron-6P, even at high dosages. Our data suggest that the Omicron-specific mRNA vaccine is highly effective and safe in animal models and provides long-term immunologic protection against SARS-CoV-2 Omicron infections.