Metallaphotocatalytic Amination of Aryl Chlorides Enabled by Highly Crystalline Acetylene-Based Hydrazone-Linked Covalent Organic Frameworks.

Amination of aryl chlorides by metallaphotocatalysis is highly desired but remains practically challenging. Meanwhile, relying on soluble noble-metal photocatalysts suffers from resource scarcity and structural instability which limit their practical application. Here in, a highly crystalline acetylene-based hydrazone-linked covalent organic framewok-1 (AC-COF-1) is reported that enables metallaphotocatalytic amination of aryl chlorides. The non-planar effect of hydrazone linkage and weak interlayer attraction of acetylene bond are minimized by intralayer hydrogen-bonding. As a result, the COF shows not only improved crystallinity and porosity, but also enhanced optical and electronic properties compared to a COF analog without hydrogen-bonding. Notably, dual AC-COF-1/Ni system affords CN coupling products from broad aryl chloride substrates in excellent yields (up to 99%) and good functional tolerance. Furthermore, AC-COF-1 is recoverable and reusable for seven times photocatalysis cycles. This report demonstrates simple approach to tune the structure-activity relationship in COFs at molecular level.

Inhalable nanovaccine with biomimetic coronavirus structure to trigger mucosal immunity of respiratory tract against COVID-19.

The COVID-19 pandemic caused by SARS-CoV-2 seriously threatens global public health. It has previously been confirmed that SARS-CoV-2 is mainly transmitted between people through "respiratory droplets". Therefore, the respiratory tract mucosa is the first barrier to prevent virus invasion. It is very important to stimulate mucosal immunity to protect the body from respiratory virus infection. Inspired by this, we designed a bionic-virus nanovaccine, which can induce mucosal immunity by nasal delivery to prevent virus infection from respiratory tract. The nanovaccine that mimic virosome is composed of poly(I:C) mimicking viral genetic material as immune adjuvant, biomimetic pulmonary surfactant (bio-PS) liposomes as capsid structure of virus and the receptor binding domains (RBDs) of SARS-CoV-2 as "spike" to completely simulate the structure of the coronavirus. The nanovaccine can be administered by inhaling to imitate the process of SARS-CoV-2 infection through the respiratory tract. Our results demonstrated that the inhalable nanovaccine with bionic virus-like structure has a stronger mucosal protective effect than routine muscle and subcutaneous inoculation. In particular, high titer of secretory immunoglobulin A (sIgA) was detected in respiratory secretions, which effectively neutralize the virus and prevent it from entering the body through the respiratory tract. Through imitating the structure and route of infection, this inhalable nanovaccine strategy might inspire a new approach to the precaution of respiratory viruses.

Ultrasound-Remote Selected Activation Mitophagy for Precise Treatment of Rheumatoid Arthritis by Two-Dimensional Piezoelectric Nanosheets.

Excess reactive oxygen species (ROS) produced by abnormal mitochondria is one of the critical triggers of rheumatoid arthritis (RA). Existing nanocatalytic therapies can only catalyze the breakdown of ROS but cannot address the root cause of ROS production, i.e., abnormal mitochondria. Here, we designed an ultrasound (US) piezoelectric catalytic therapy, which can induce mitophagy in a spatiotemporally controlled manner to treat RA. The prepared two-dimensional piezoelectric nanosheets (NSs) Fe/BiOCl with US catalytic activity can efficiently generate electrons under US stimulation to meet the purpose of consuming H+ in the outer mitochondrial membrane and disturbing the H+ supply in the mitochondrial matrix. This causes depolarization of the mitochondrial membrane potential (MMP), triggering the autophagy of mitochondria in regions of inflammation to eliminate the source of ROS regeneration. Analysis of cellular and RA model-related experiments showed that piezoelectric US-catalyzed therapy involving Fe/BiOCl NSs alleviated RA by inducing mitophagy. This provides an explanation of the mechanism for piezoelectric US catalytic therapy and suggests promising strategies for biomedical applications of US piezoelectric materials.

Single-Atom Nanocatalytic Therapy for Suppression of Neuroinflammation by Inducing Autophagy of Abnormal Mitochondria.

Catalysts have achieved efficacy in scavenging reactive oxygen species (ROS) to eliminate neuroinflammation, but it ignores the essential fact of blocking the source of ROS regeneration. Here, we report the single-atom catalysts (SACs) Pt/CeO2, which can effectively catalyze the breakdown of existing ROS and induce mitochondrial membrane potential (Δψm) depolarization by interfering with the α-glycerophosphate shuttle pathway and malate-aspartate shuttle pathway, indirectly triggering the self-clearance of dysfunctional mitochondria and thus eradicating the source of ROS generation. In a therapeutic model of Parkinson's disease (PD), Pt/CeO2 wrapped by neutrophil-like (HL-60) cell membranes and modified by rabies virus glycoprotein (RVG29) effectively crosses the blood-brain barrier (BBB), enters dopaminergic neurons entering the neuroinflammatory region breaking down existing ROS and inducing mitophagy by electrostatic adsorption targeting mitochondria to prevent ROS regeneration after catalyst discharge. This strategy of efficiently eliminating ROS at the lesion and fundamentally blocking the source of ROS production can address both symptoms and root causes and provides a mechanism of explanation and action target for the treatment of inflammation-related diseases.

Acyclic Cucurbit[n]urils: Effective Taste Masking Nanocontainers for Cationic Bitter Compounds.

New acyclic cucurbit[n]urils (ACBs) with eight carboxylate groups were synthesized. These hosts are highly soluble in water, and can form stable inclusion complexes with cationic bitter compounds. ACBs are confirmed to be non-toxic and biocompatible. Two-bottle preference (TBP) tests on mice show that all ACBs are tasteless to mammals. ACBs are discovered to mask the bitterness of berberine and denatonium benzoate, but not quinine hydrochloride, due to different binding modes.

Sendai virus-based immunoadjuvant in hydrogel vaccine intensity-modulated dendritic cells activation for suppressing tumorigenesis.

The conventional immunoadjuvants in vaccine have weak effect on stimulating antigen presentation and activating anti-tumor immunity. Unexpectedly, we discovered that non-pathogenic Sendai virus (SeV) could activate antigen-presenting cells (APCs) represented by dendritic cells (DCs). Here, we designed an injectable SeV-based hydrogel vaccine (SHV) to execute multi-channel recruitment and stimulation of DCs for boosting the specific immune response against tumors. After the release of the NIR-triggered antigens from tumor cells, dendritic cells around the vaccine efficiently transport the antigens to lymph nodes and present them to T lymphocytes, thereby inducing systemic anti-tumor immune memory. Our findings demonstrated that the SHV with excellent universality, convenience and flexibility has achieved better immune protection effects in inhibiting the occurrence of melanoma and breast cancer. In conclusion, the SHV system might serve as the next generation of personalized anti-tumor vaccines with enhanced features over standard vaccination regimens, and represented an alternative way to suppress tumorigenesis.

Nanoarmour-shielded single-cell factory for bacteriotherapy of Parkinson's disease.

Cell-based therapy for Parkinson's disease (PD) is a novel and promising approach in recent years. However, exogenous cells are easy to be captured and destroyed by the harsh environment in vivo, so their application prospects have been severely limited. Here, a facile yet versatile approach for decorating individual living cells with nano-armor coatings is reported. By simply self-assembly with liposome under a cyto-compatible condition, the lipid bimolecular coating on the surface of each cell acts as armor to effectively protect it from the attack and destruction of strong acids and digestive enzymes during the oral treatment of PD. Our results demonstrated that the liposome coated B. adolescentis (LCB) could significantly improve the colonization rate in the intestinal tract. LCB, as a living cell factory, can self-regulate to produce a constant concentration of γ-aminobutyric acid and maintain a longer half-life for the treatment of PD. Then, we also explored the specific mechanism of LCB to improve the behavior of murine models of PD, including abating inflammatory effects, reducing neuronal apoptosis, regulating the activity of dopaminergic neurons and microglia. The simple nano-armor shielded single-cell factory can produce neurotransmitters-like drugs on demand in vivo, introducing novel strategies of integration of producing and using to the research of drug delivery field.