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 is used as a “spike”, so as 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.
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.
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