Inhaled SARS-CoV-2 vaccine for single-dose dry powder aerosol immunization.

The COVID-19 pandemic has fostered major advances in vaccination technologies1-4; however, there are urgent needs for vaccines that induce mucosal immune responses and for single-dose, non-invasive administration4-6. Here we develop an inhalable, single-dose, dry powder aerosol SARS-CoV-2 vaccine that induces potent systemic and mucosal immune responses. The vaccine encapsulates assembled nanoparticles comprising proteinaceous cholera toxin B subunits displaying the SARS-CoV-2 RBD antigen within microcapsules of optimal aerodynamic size, and this unique nano-micro coupled structure supports efficient alveoli delivery, sustained antigen release and antigen-presenting cell uptake, which are favourable features for the induction of immune responses. Moreover, this vaccine induces strong production of IgG and IgA, as well as a local T cell response, collectively conferring effective protection against SARS-CoV-2 in mice, hamsters and nonhuman primates. Finally, we also demonstrate a mosaic iteration of the vaccine that co-displays ancestral and Omicron antigens, extending the breadth of antibody response against co-circulating strains and transmission of the Omicron variant. These findings support the use of this inhaled vaccine as a promising multivalent platform for fighting COVID-19 and other respiratory infectious diseases.

On-column capping of poly dT media-tethered mRNA accomplishes high capping efficiency, enhanced mRNA recovery, and improved stability against RNase.

The messenger RNA (mRNA) 5'-cap structure is indispensable for mRNA translation initiation and stability. Despite its importance, large-scale production of capped mRNA through in vitro transcription (IVT) synthesis using vaccinia capping enzyme (VCE) is challenging, due to the requirement of tedious and multiple pre-and-post separation steps causing mRNA loss and degradation. Here in the present study, we found that the VCE together with 2'-O-methyltransferase can efficiently catalyze the capping of poly dT media-tethered mRNA to produce mRNA with cap-1 structure under an optimized condition. We have therefore designed an integrated purification and solid-based capping protocol, which involved capturing the mRNA from the IVT system by using poly dT media through its affinity binding for 3'-end poly-A in mRNA, in situ capping of mRNA 5'-end by supplying the enzymes, and subsequent eluting of the capped mRNA from the poly dT media. Using mRNA encoding the enhanced green fluorescent protein as a model system, we have demonstrated that the new strategy greatly simplified the mRNA manufacturing process and improved its overall recovery without sacrificing the capping efficiency, as compared with the conventional process, which involved at least mRNA preseparation from IVT, solution-based capping, and post-separation and recovering steps. Specifically, the new process accomplished a 1.76-fold (84.21% over 47.79%) increase in mRNA overall recovery, a twofold decrease in operation time (70 vs. 140 min), and similar high capping efficiency (both close to 100%). Furthermore, the solid-based capping process greatly improved mRNA stability, such that the integrity of the mRNA could be well kept during the capping process even in the presence of exogenously added RNase; in contrast, mRNA in the solution-based capping process degraded almost completely. Meanwhile, we showed that such a strategy can be operated both in a batch mode and in an on-column continuous mode. The results presented in this work demonstrated that the new on-column capping process developed here can accomplish high capping efficiency, enhanced mRNA recovery, and improved stability against RNase; therefore, can act as a simple, efficient, and cost-effective platform technology suitable for large-scale production of capped mRNA.

Advancement of Engineered Bacteria for Orally Delivered Therapeutics.

The use of bacteria and their biotic components as therapeutics has shown great potential in the treatment of diseases. Orally delivered bacteria improve patient compliance compared with injection-administered bacteria and are considered the preferred mode. However, due to the harsh gastrointestinal environment, the viability and therapeutic efficacy of orally delivered bacteria are significantly reduced in vivo. In recent years, with the rapid development of synthetic biology and nanotechnology, bacteria and biotic components have been engineered to achieve directed genetic reprogramming for construction and precise spatiotemporal control in the gastrointestinal tract, which can improve viability and therapeutic efficiency. Herein, a state-of-the-art review on the current progress of engineered bacterial systems for oral delivery is provided. The different types of bacterial and biotic components for oral administration are first summarized. The engineering strategies of these bacteria and biotic components and their treatment of diseases are next systematically summarized. Finally, the current challenges and prospects of these bacterial therapeutics are highlighted that will contribute to the development of next-generation orally delivered bacteriotherapy.

Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations.

BACKGROUND: Gastric cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal. RESULTS: Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route. CONCLUSIONS: This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy.

Advances in encapsulating gonadotropin-releasing hormone agonists for controlled release: a review.

Gonadotropin-releasing hormone (GnRH) agonists are peptides consisting of nine or ten amino acid residues. GnRH agonists have been applied in the therapy of sexual hormone disorders like prostate cancer, endometriosis, uterine myoma, central precious puberty, and in-vitro fertility. Treatment is achieved by continuous hormone intake and long-term agonists administration, which is usually associated with poor patient compliance. Because GnRH agonists that are administered with the parenteral route are broken down by peptidase, their half-life is short. As a result, developing sustained release for the drug delivery system is significant. Even though some drugs have been successfully delivered with long-acting release microspheres and approved by the Food and Drug Administration (FDA), some challenges remain. This review highlighted current approaches to encapsulate GnRH agonists into delivery systems and strategies encountered during the loading process. Moreover, the following sections provide strategies to improve the release profile, and animal and human studies were summarised.

Synthetic Particles for Cancer Vaccines: Connecting the Inherent Supply Chain.

Cancer vaccines have opened a new paradigm for safe and effective antitumor therapy, but they still suffer from shortcomings such as insufficient immunogenicity and immune tolerance, which seldom makes them the first choice in clinic. In fact, similar to providing a high-end product, a robust antitumor effect depends on the inherent supply chain, which attains, processes, and presents tumor-associated antigens via antigen presenting cells to T cells, which then leads to lysis of the cancer cells to release more antigens to complete the supply chain. Under these circumstances, the failure of cancer vaccines can be treated as a blockade or chain rupture. Thus, for effective tumor treatment, the key is to rationally design logistic systems to restore the supply chain.Under these circumstances, this Account summarizes our recent attempts to exploit the immunogenic trait of synthetic particles to enhance the distribution, presentation, and immune activations of the whole priming process in cancer vaccines: (1) Raw material (tumor antigen/signals) procurement: We illustrated the efforts to deliver antigens to antigen presenting cells (APCs) and draining lymph nodes for potent internalizations, and put more emphasis on the structural effect of sizes, charges, shapes, and assembly strategies for the antigen depot, lymph node transfer, and APC endocytosis. (2) Manufacture of cytotoxic T lymphocytes (CTLs) via APC recognition and presentation: We centered on exploiting the softness of two-dimensional graphene and Pickering emulsions to dynamically potentiate the immune recognition, and demonstrating the recent advances in lysosome escape strategies for enhanced antigen cross-presentations. (3) Marketing the accumulations of CTLs and the reversal of an immunosuppressive microenvironment within the tumor: We demonstrated the previous attempts to inherently cultivate the tumor tropism of the T cells via the multiantigenic repertoire and discussed the advances and challenges of combinatory cancer vaccines with an immune checkpoint blockade to reinforce the antitumor efficacy. Collectively, this Account aims to illustrate the potential of the particulate cancer vaccines to recapitalize the inherent host immune responses for the maximum antitumor effect. And by integrating the antitumor supply chain, optimized synthetic particles may shed light on the development of safe and effective particulate cancer vaccines.

Tailored nanodisc immobilization for one-step purification and reconstitution of cytochrome P450: A tool for membrane proteins' hard cases.

A novel nanodisc-based immobilization method was developed for high-efficient purification and reconstitution of cytochrome P450 in one step. Using membrane scaffold protein containing a histidine tag, charged-nanodiscs were prepared in the form of self-assembly of lipid-protein nanoparticles. Their properties including the particle diameter and its distribution and Zeta potential were controlled well by adjusting molar ratios of phospholipids to membrane scaffold protein. At an optimum lipid-to-membrane scaffold protein molar ratio of 60:1, uniformly regular-shaped and discoidal nanodiscs with an average particle diameter of 10 nm and Zeta potential of -19 mV were obtained. They can be well fractionated by size exclusion chromatography. Charged-nanodiscs were successfully immobilized onto Ni-chelating microspheres via histidine tags with a density of 6.6 mg membrane scaffold protein/mL gel. After being packed in a column, chromatography studies demonstrated that this nanodisc-immobilized chromatographic medium had a specific binding to cytochrome P450 in rat liver microsome. Nanodiscs containing cytochrome P450 can be furthermore eluted from the column with a diameter of about 87.0 nm and height of about 8.0 nm, respectively. The purity of cytochrome P450 after purification increased 25 folds strikingly. This nanodisc-immobilized chromatography method is promising for the one-step purification and reconstitution of membrane protein.

An Apoferritin-Hemagglutinin Conjugate Vaccine with Encapsulated Nucleoprotein Antigen Peptide from Influenza Virus Confers Enhanced Cross Protection.

Naturally occurring self-assembling ferritin nanoparticles have become widely appreciated for vaccine design. In this study, an apoferritin (AFt) nanocage was used as a carrier to construct a biomimetic influenza vaccine by encapsulating a conserved internal nucleoprotein (NP) antigen peptide inside the nanocage, followed by chemically conjugating the surface antigen hemagglutinin (HA) protein on the outer surface of the AFt. Benefiting from the excellent thermal stability and thermallyassociated structural flexibility of the AFt nanocages, a novel temperature shift based encapsulation process was proposed and proved efficient for encapsulation of the NP peptides. On average, about 18 NPs were encapsulated and 1.6 HA antigens were conjugated in each of the HA-AFt+NP dual-antigen influenza vaccines. Upon immunization in mice, the HA-AFt+NP vaccine elicited both HA and NP-specific antibodies, and conferred complete protection against a lethal infection of both homologous PR8 H1N1 and heterologous A/FM/1/47 (FM1, H1N1) strains, while the HA-AFt conjugate vaccine without encapsulated NP antigen only conferred 60% protection against the FM1 H1N1 viral challenge. The potential cross-protective effect of the HA-AFt+NP vaccine was further demonstrated by significant specific hemagglutination inhibition (HAI) titers in serum of the immunized mice against heterologous A/Hong Kong/4801/2014 (H3N2) viral strain, which was about 3-fold of that induced by HA antigen and 2-fold of the HA-AFt conjugate vaccine. This biomimetic HA-AFt+NP conjugate vaccine, therefore, may represent a new strategy for developing a potential universal influenza vaccine without the need of any adjuvant, and further broaden the application of AFt nanocages in the areas of vaccine development and delivery system.

A Novel Particulate Delivery System Based on Antigen-Zn2+ Coordination Interactions Enhances Stability and Cellular Immune Response of Inactivated Foot and Mouth Disease Virus.

The interactions between antigen and adjuvant were among the most significant factors influencing the immunogenicity of vaccines, especially for unstable antigens like inactivated foot and mouth disease virus (iFMDV). Here we propose a novel antigen delivery pattern based on the coordination interaction between transition metal ions Zn2+ chelated to chitosan nanoparticles and iFMDV, which is known to be rich in histidine. The zinc chelated chitosan particles (CP-PEI-Zn) were prepared by cross-linking chitosan particles (CP) with sodium tripolyphosphate (TPP), modifying with metal chelator polyethylenimine (PEI), and subsequent chelating of Zn2+. The coordination interaction was confirmed by analyzing the adsorption and desorption behavior of iFMDV on CP-PEI-Zn by high-performance size exclusion chromatography (HPSEC), while the CP-PEI without chelating Zn2+ loads iFMDV mainly through electrostatic interactions. The iFMDV loaded on CP-PEI-Zn showed better thermal stability than that on CP-PEI, as revealed by a slightly higher transition temperature (Tm) related to iFMDV dissociation. After subcutaneous immunization in female Balb/C mice, antigens loaded on CP-PEI and CP-PEI-Zn all induced higher specific antibody titers, better activation of B lymphocytes, and more effector-memory T cells proliferation than the free antigen and iFMDV adjuvanted with ISA 206 emulsion did. Moreover, CP-PEI-Zn showed superior efficacy to CP-PEI in promoting the proliferation of effector-memory T cells and secretion of cytokines, indicating a more potent cellular immune response. In summary, the CP-PEI-Zn stabilized the iFMDV after loading and promoted both humoral and cellular immune responses, thus reflecting its potential to be a promising adjuvant for the iFMDV vaccine and other unstable viral antigens.

Cell Membrane Camouflaged Hydrophobic Drug Nanoflake Sandwiched with Photosensitizer for Orchestration of Chemo-Photothermal Combination Therapy.

Many candidate anticancer drugs have suffered from their intrinsic hydrophobicity, which poses several obstacles for clinical application. To overcome this challenge and further improve the performance, herein a nanocrystal-based biomimetic formulation with a sandwich structure is developed. As the core, flake shaped nanocrystals (NCs) with high loading of the hydrophobic drug hydroxycamptothecin (HCPT) are synthesized via a mild nanoprecipitation process by exploring the template effect of serum albumin. Meanwhile, the camouflaged cancer cell membrane (CM) composed of plentiful membrane proteins endows the NCs with homotypic targeting capacity at tumor sites. In addition, the photosensitizer indocyanine green sandwiched between NCs and CM not only converts near infrared light to heat for photothermal treatment but also improves the dissolution of HCPT NCs for chemotherapy. These features corporately achieve the orchestration of chemo-photothermal combination therapy and completely inhibit tumor growth with few adverse effects, showing promise as a new modality for the utilization of hydrophobic drugs to treat cancer.

Exploiting the pliability and lateral mobility of Pickering emulsion for enhanced vaccination.

A major challenge in vaccine formulations is the stimulation of both the humoral and cellular immune response for well-defined antigens with high efficacy and safety. Adjuvant research has focused on developing particulate carriers to model the sizes, shapes and compositions of microbes or diseased cells, but not antigen fluidity and pliability. Here, we develop Pickering emulsions-that is, particle-stabilized emulsions that retain the force-dependent deformability and lateral mobility of presented antigens while displaying high biosafety and antigen-loading capabilities. Compared with solid particles and conventional surfactant-stabilized emulsions, the optimized Pickering emulsions enhance the recruitment, antigen uptake and activation of antigen-presenting cells, potently stimulating both humoral and cellular adaptive responses, and thus increasing the survival of mice upon lethal challenge. The pliability and lateral mobility of antigen-loaded Pickering emulsions may provide a facile, effective, safe and broadly applicable strategy to enhance adaptive immunity against infections and diseases.

Positively Charged Polyprodrug Amphiphiles with Enhanced Drug Loading and Reactive Oxygen Species-Responsive Release Ability for Traceable Synergistic Therapy.

Due to the vast differences in chemical properties among small molecule drugs, nucleotide drugs, and superparamagnetic iron oxide nanocubes (SPIONs), such as charge and hydrophobicity, entrapment of these within a single carrier for traceable synergistic therapy has been proven difficult. Herein, we synthesize positively charged polyprodrug amphiphiles. The hydrophobic polyprodrug unit of the amphiphiles is positively charged, which can simultaneously load hydrophobic SPIONs and absorb negative let-7b antisense oligonucleotide to construct traceable co-delivery nanoparticles (NPs). This characteristic avoids the use of inert materials and enhances drug loading of the traceable NPs. The traceable NPs can achieve controlled release of drugs to reduce the differentiation of exogenous neural stem cells (NSCs) and enhance their secretion of brain-derived neurotrophic factor (BDNF) synergistically. Exogenous NSCs treated with the NPs significantly rescue the memory deficits in 2xTg-AD mice. In addition, the transplantation site and migration of exogenous NSCs can be traced using the SPIONs with high r2 value for magnetic resonance imaging. Therefore, traceable NPs self-assembled from the positively charged polyprodrug amphiphiles may have the potential to open up a new avenue for treatment of Alzheimer's disease (AD), as well as other neurodegenerative disorders.

Exploration of Antigen Induced CaCO3 Nanoparticles for Therapeutic Vaccine.

Therapeutic vaccines possess particular advantages and show promising potential to combat burdening diseases, such as acquired immunodeficiency syndrome, hepatitis, and even cancers. An efficient therapeutic vaccine would strengthen the immune system and eventually eliminate target cells through cytotoxic T lymphocytes (CTLs). Unfortunately, insufficient efficacy in triggering such an adaptive immune response is a problem that remains unsolved. To achieve efficient cellular immunity, antigen-presenting cells must capture and further cross-present disease-associated antigens to CD8 T cells via major histocompatibility complex I molecules. Here, a biomimetic strategy is developed to fabricate hierarchical ovalbumin@CaCO3 nanoparticles (OVA@NP, ≈500 nm) under the templating effect of antigen OVA. Taking advantage of the unique physicochemical properties of crystalline vaterite, cluster structure, and high loading, OVA@NP can efficiently ferry cargo antigen to dendritic cells and blast lysosomes for antigen escape to the cytoplasm. In addition, the first evidence that the physical stress from generated CO2 induces autophagy through the LC3/Beclin 1 pathways is presented. These outcomes cooperatively promote antigen cross-presentation, elicit CD8 T cell proliferation, ignite a potent and specific CTL response, and finally achieve prominent tumor therapy effects.

Uniform polysaccharide composite microspheres with controllable network by microporous membrane emulsification technique.

High resolution has been constantly pursued in both preparative and analytical chromatography. Chromatographic media are a key factor during the entire separation process. Tailor-made chromatographic media have gained more attention because of their adjustable structure appropriate for application. Uniform polysaccharide composite microspheres were prepared with a mixture of agarose and dextran solution by membrane emulsification technique for the first time. Their pore structure was deliberately regulated by adjusting both the polysaccharide composition and the molecular weight of dextran. Compared with pure agarose microspheres, polysaccharide composite microspheres had a higher separation resolution and their separation range was controllable. By increasing agarose concentration and decreasing dextran concentration at the same time during the preparation of composite microspheres, the mean pore size increased first and then decreased later, and also the pore size distribution became narrower. By increasing the molecular weight of dextran, the pores became smaller with a narrower pore size distribution. Microspheres with a composition of 10% agarose/2% dextran T40 or 8% agarose/4% dextran T150 showed a higher separation resolution for proteins within range of low molecular weight. Furthermore, the mechanical strength of this composite microsphere was improved by adjusting its composition. Atomic force microscope (AFM) results showed that pores were distributed evenly on both the surface and the inner part of microspheres, beneficial for the passage of biomolecules. These novel uniform polysaccharide composite microspheres have great potential for high-resolution bioseparation. Graphical abstract ᅟ.

Potential probiotic characterization of Lactobacillus reuteri from traditional Chinese highland barley wine and application for room-temperature-storage drinkable yogurt.

The aim of this study was to select probiotic strains that could be used in drinkable yogurt to yield viable cells following storage at room temperature (RT). The uniquely high altitude conditions in Tibet and the alcoholic environment of certain products, such as the highland barley wine homemade in Tibet, may induce unusual characteristics of microbial strains. A total of 27 lactic acid bacteria were isolated from homemade highland barley wines. One strain, Lactobacillus reuteri WHH1689, demonstrated no ability for lactose utilization, exhibited a high survival rate during storage at RT in drinkable yogurts, and produced very weak post-acidification. This strain showed great resistance to conditions simulating the gastrointestinal tract, including strong adherence to HT-29 cells and inhibitory activity against Escherichia coli, Shigella flexneri, Salmonella paratyphi ß, and Staphylococcus aureus. A dextran sulfate sodium (DSS)-induced mouse model was used to evaluate the in vivo influence of Lb. reuteri WHH1689 on the intestinal flora and showed that strain WHH1689 increased viable counts of bifidobacteria in feces of mice. The probiotic strain selected in this study-with its high survival at RT and lack of serious post-acidification problems-may provide significant improvements for dairy industry products by extending the storage time of dairy products with living cells.

Adjuvanticity Regulation by Biodegradable Polymeric Nano/microparticle Size.

Polymeric nano/microparticles as vaccine adjuvants have been researched in experimental and clinical studies. A more profound understanding of how the physicochemical properties regulate specific immune responses has become a vital requirement. Here we prepared poly(d,l-lactic-co-glycolic acid) (PLGA) nano/microparticles with uniform sizes (500 nm, 900 nm, 2.1 µm, and 4.9 µm), and the size effects on particle uptake, activation of macrophages, and antigen internalization were evaluated. Particle uptake kinetic studies demonstrated that 900 nm particles were the easiest to accumulate in cells. Moreover, they could induce macrophages to secrete NO and IL-1ß and facilitate antigen internalization. Furthermore, 900 nm particles, mixed with antigen, could exhibit superior adjuvanticity in both humoral and cellular immune responses in vivo, including offering the highest antibody protection, promoting the maximum secretion levels of IFN-γ and IL-4 than particles with other sizes. Overall, 900 nm might be the optimum choice for PLGA particle-based vaccine adjuvants especially for recombinant antigens. Understanding the effect of particle size on the adjuvanticity based immune responses might have important enlightenments for rational vaccine design and applications.

Precise control of agarose media pore structure by regulating cooling rate.

A porous structure is the key factor to successful chromatography separation. Agarose gel as one of the most popular porous media has been extensively used in chromatography separation. As the cooling process in the agarose gelation procedure can directly influence the pore structure, ten kinds of 4% agarose media with different cooling rates from 0.132 to 16.7°C/min were synthesized, and the pore structure was determined accurately by using low-field NMR spectroscopy. The curves of pore structure and cooling rate can be divided into two stages with the boundary of 6°C/min. In stage I, the pore structure met a power equation with the decrease of the cooling rate, and in stage II, the process reached a plateau. Confirmatory experiments proved that, by adjusting the cooling rate, a precise control of the pore structure of agarose media can be realized, furthermore, cooling rate optimization was an effective way to control the pore size of agarose media and can further tailor the pore structure for more effective separation of different proteins.

Enhanced binding by dextran-grafting to Protein A affinity chromatographic media.

Dextran-grafted Protein A affinity chromatographic medium was prepared by grafting dextran to agarose-based matrix, followed by epoxy-activation and Protein A coupling site-directed to sulfhydryl groups of cysteine molecules. An enhancement of both the binding performance and the stability was achieved for this dextran-grafted Protein A chromatographic medium. Its dynamic binding capacity was 61 mg immunoglobulin G/mL suction-dried gel, increased by 24% compared with that of the non-grafted medium. The binding capacity of dextran-grafted medium decreased about 7% after 40 cleaning-in-place cycles, much lower than that of the non-grafted medium as decreased about 15%. Confocal laser scanning microscopy results showed that immunoglobulin G was bound to both the outside and the inside of dextran-grafted medium faster than that of non-grafted one. Atomic force microscopy showed that this dextran-grafted Protein A medium had much rougher surface with a vertical coordinate range of ±80 nm, while that of non-grafted one was ±10 nm. Grafted dextran provided a more stereo surface morphology and immunoglobulin G molecules were more easily to be bound. This high-performance dextran-grafted Protein A affinity chromatographic medium has promising applications in large-scale antibody purification.

Recent Studies of Pickering Emulsions: Particles Make the Difference.

In recent years, emulsions stabilized by micro- or nanoparticles (known as Pickering emulsions) have attracted much attention. Micro- or nanoparticles, as the main components of the emulsion, play a key role in the preparation and application of Pickering emulsions. The existence of particles at the interface between the oil and aqueous phases affects not only the preparation, but also the properties of Pickering emulsions, affording superior stability, low toxicity, and stimuli-responsiveness compared to classical emulsions stabilized by surfactants. These advantages of Pickering emulsions make them attractive, especially in biomedicine. In this review, the effects of the characteristics of micro- and nanoparticles on the preparation and properties of Pickering emulsions are introduced. In particular, the preparation methods of Pickering emulsions, especially uniform-sized emulsions, are listed. Uniform Pickering emulsions are convenient for both mechanistic research and applications. Furthermore, some biomedical applications of Pickering emulsions are discussed and the problems hindering their clinical application are identified.

Integration of Artificial Photosynthesis System for Enhanced Electronic Energy-Transfer Efficacy: A Case Study for Solar-Energy Driven Bioconversion of Carbon Dioxide to Methanol.

Biocatalyzed artificial photosynthesis systems provide a promising strategy to store solar energy in a great variety of chemicals. However, the lack of direct interface between the light-capturing components and the oxidoreductase generally hinders the trafficking of the chemicals and photo-excited electrons into the active center of the redox biocatalysts. To address this problem, a completely integrated artificial photosynthesis system for enhanced electronic energy-transfer efficacy is reported by combining co-axial electrospinning/electrospray and layer-by-layer (LbL) self-assembly. The biocatalysis part including multiple oxidoreductases and coenzymes NAD(H) was in situ encapsulated inside the lumen polyelectrolyte-doped hollow nanofibers or microcapsules fabricated via co-axial electrospinning/electrospray; while the precise and spatial arrangement of the photocatalysis part, including electron mediator and photosensitizer for photo-regeneration of the coenzyme, was achieved by ion-exchange interaction-driven LbL self-assembly. The feasibility and advantages of this integrated artificial photosynthesis system is fully demonstrated by the catalyzed cascade reduction of CO2 to methanol by three dehydrogenases (formate, formaldehyde, and alcohol dehydrogenases), incorporating the photo-regeneration of NADH under visible-light irradiation. Compared to solution-based systems, the methanol yield increases from 35.6% to 90.6% using the integrated artificial photosynthesis. This work provides a novel platform for the efficient and sustained production of a broad range of chemicals and fuels from sunlight.