Sonodynamic therapy (SDT) is a non‐invasive and highly penetrating treatment strategy under ultrasound irradiation. However, uncertainty in the mechanism of SDT has seriously hindered its future clinical application. Here, the mechanism of SDT enhanced by the wettability of nanoparticles is investigated. Nanoparticles can adsorb and stabilize nanobubbles in liquid, thus enhancing SDT efficiency. The stability of the nanobubbles is positively correlated with the desorption energy of the nanoparticles, which is determined by the wettability of the nanoparticles. This conclusion is verified for mesoporous silica and polystyrene nanoparticles and it is found that nanoparticles with a water contact angle of about 90° possess the largest desorption energy. To further apply this conclusion, thrombus models are constructed on rats and the experimental results demonstrate that nanoparticles with the largest desorption energy have the highest thrombolytic efficiency. It is believed that these findings will help to better understand the SDT mechanism and guide new strategies for rational design of nanoparticles adopted in SDT.
Photothermal therapy based on conjugated polymers represents a promising antibacterial strategy but still possesses notable limitations. Herein, degradable pseudo conjugated polymers (PCPs) containing photothermal molecular backbones and reactive oxygen species (ROS)-sensitive thioketal bonds are designed. Triphenylphosphine (PPh 3 ) is introduced into PCPs to generate phosphonium-based PCPs (pPCPs), which further assembled with hyaluronic acid into pPCP nanoparticles (pPCP-NPs). pPCP-NPs with quaternary phosphonium cations selectively anchor on and destroy bacterial cell membranes through electrostatic action. Under 1064 nm laser irradiation, pPCP-NPs (pPCP-NPs/+L) produce near-infrared-II (NIR-II) photothermal antibacterial effect, thereby killing bacteria in a sustained manner. pPCP-NPs are readily degraded upon ROS abundant at infection sites, therefore exhibiting enough biosafety. pPCP-NPs/+L display an almost 100% bacterial inhibition rate in vitro and resultin a nearly complete recovery of bacteria-induced mouse wounds. A further metabolomics analysis denotes that pPCP-NPs/+L work in a concerted way to induce bacterial DNA damage, inhibit bacterial carbon/nitrogen utilization and amino acid/nucleotide synthesis. Taken together, degradable pPCP-NPs with both NIR-II photothermal effect and cationic phosphonium structural bacteriostasis provide a new avenue for antibiotics-alternative anti-infection therapy.
Clinical therapy of multidrug resistant (MDR) bacteria‐induced deep‐tissue infections such as pneumonia is highly challenging. Ultrasound (US)‐induced sonodynamic therapy (SDT) is a promising strategy for treatment of deep‐tissue diseases given the strong tissue penetration of US. Here, ZIF‐8‐derived carbon@TiO2 nanoparticles (ZTNs) are developed as inhalable sonosensitizers for bacterial pneumonia. ZTNs upon US irradiation exhibit an excellent efficacy to produce reactive oxygen species (ROS) and thereby to kill Gram‐negative MDR bacteria in vitro. Taking advantage of aerosolized intratracheal inoculation, ZTNs can be precisely delivered to lung infection sites, and display an effective SDT‐based elimination of Gram‐negative MDR bacteria in the lung infection models of immunocompetent or immunodeficient mice. Particularly, ZTNs upon US irradiation give a 100% survival rate in the severely immunodeficient NOD/SCID mice with a lethal bacterial pneumonia. In addition, ZTNs have no obvious toxicity at both cellular and animal levels. Metal–organic‐framework‐derived nanoparticles as safe and efficient inhalable sonosensitizer have a great potential to be used for the clinical antibiotics‐alternative treatment of MDR bacterial pneumonia. This study presents a new paradigm for SDT‐based treatment of deep‐tissue bacterial infections, and will expand the nanomedicine application of inorganic sonosensitizers.
A series of CO 2 -tolerant dual-phase dense oxygen permeable membranes of stoichiometry Ce 0.8 Gd 0.2 O 2−δ − Ba 0.95 La 0.05 Fe 1−x Nb x O 3−δ (CG−BLF 1−x N x , x = 0, 0.025, 0.05, 0.10, and 0.15) were designed and prepared by the sol−gel method. Their stability regarding phase composition and structure, oxygen permeability, and CO 2 -tolerant property were investigated by X-ray diffraction (XRD), thermogravimetry and differential scanning calorimetry (TG-DSC), and temperature-programmed desorption of oxygen (O 2 -TPD). Results of the materials characterization showed excellent chemical compatibility between CG and BLF 1−x N x without the formation of any impurity phase after sintering at 1200°C in air. The oxygen-permeation experiments showed that with increasing niobium content, the oxygen permeability of the CG−BLF 1−x N x membranes decreased slightly, but the compositional and structural stability in CO 2 atmosphere improved significantly. The 60 wt % CG−40 wt % BLF 0.9 N 0.1 membrane showed simultaneously good oxygen permeability and excellent CO 2 tolerance, and the oxygen-permeation flux reached 0.195 mL·cm −2 ·min −1 in pure CO 2 atmosphere at 925°C using a 1.0 mm thick membrane. This work demonstrates that CG−BLF 1−x N x dual-phase membranes have great application potential for separating oxygen from highly concentrated CO 2 atmosphere.
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