Biomimetic Self-Propelled Asymmetric Nanomotors for Cascade-Targeted Treatment of Neurological Inflammation.

The precise targeted delivery of therapeutic agents to deep regions of the brain is crucial for the effective treatment of various neurological diseases. However, achieving this goal is challenging due to the presence of the blood‒brain barrier (BBB) and the complex anatomy of the brain. Here, a biomimetic self-propelled nanomotor with cascade targeting capacity is developed for the treatment of neurological inflammatory diseases. The self-propelled nanomotors are designed with biomimetic asymmetric structures with a mesoporous SiO2 head and multiple MnO2 tentacles. Macrophage membrane biomimetic modification endows nanomotors with inflammatory targeting and BBB penetration abilities The MnO2 agents catalyze the degradation of H2O2 into O2, not only by reducing brain inflammation but also by providing the driving force for deep brain penetration. Additionally, the mesoporous SiO2 head is loaded with curcumin, which actively regulates macrophage polarization from the M1 to the M2 phenotype. All in vitro cell, organoid model, and in vivo animal experiments confirmed the effectiveness of the biomimetic self-propelled nanomotors in precise targeting, deep brain penetration, anti-inflammatory, and nervous system function maintenance. Therefore, this study introduces a platform of biomimetic self-propelled nanomotors with inflammation targeting ability and active deep penetration for the treatment of neurological inflammation diseases.

Effects of pulmonary-based Qigong exercise in stable patients with chronic obstructive pulmonary disease: a randomized controlled trial.

BACKGROUND: Physical exercise training is the central component of pulmonary rehabilitation. This study aimed to further investigate the rehabilitative effects of pulmonary-based Qigong exercise (PQE) in stable patients with chronic obstructive pulmonary disease (COPD). METHODS: In this randomized, assessor-blinded clinical trial, 44 participants with stable COPD were randomly assigned to 2 groups in a 1:1 ratio. Participants in the control group received usual care for 3 months. Participants in the intervention group received usual care combined with PQE (60 min each time, 2 times per day, 7 days per week, for 3 months). The outcome included exercise capacity, lung function test, skeletal muscle strength, dyspnea, and quality of life were measured before and after intervention. RESULTS: A total of 37 participants completed the trial. Compared to the control group, after 3 months of PQE, the mean change in exercise capacity, skeletal muscle strength, and quality of life were statistically significant (P < 0.05, for each), but no significant differences were observed in lung function (except for the forced expiratory volume in one second) and dyspnea (P > 0.05, for each). CONCLUSION: The findings of study suggest that the proposed program of 3 months of PQE intervention has significant improvement in exercise capacity, skeletal muscle strength, and quality of life of COPD-stable patients. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (Trial ID: ChiCTR-1800017405 on 28 July 2018; available at https://www.chictr.org.cn/showproj.html?proj=28343 ).

Effect of 12-week shen-based qigong exercise on the residual symptoms of schizophrenia: Study protocol for a single-centre randomised controlled trial.

Introduction: Negative symptoms and cognitive impairment are common residual symptoms of schizophrenia that seriously affect the quality of life and social function of patients. The intervention of residual symptoms is an important part of schizophrenia rehabilitation. Traditional Chinese exercise has been applied as a supplementary rehabilitation method for schizophrenia. However, research on its use and pertinence in the rehabilitation of residual symptoms remains lacking. In this study, we will verify the intervention effect of a new method, namely, shen-based qigong exercise, on the residual symptoms of schizophrenia, in the hopes of finding a safe and effective rehabilitation method for the residual symptoms of schizophrenia. Methods: This is a single-centre randomised controlled trial. A total of 60 schizophrenics who meet the criteria will be randomly divided into the control and intervention groups in accordance with the ratio of 1:1. Conventional drug treatment will remain unchanged in both groups. In this case, the control group will be given daily rehabilitation, whereas the intervention group will be given daily rehabilitation and shen-based qigong exercise intervention. The intervention period will be 12 weeks. The primary outcome will be negative symptoms assessed by the Scale for the Assessment of Negative Symptoms. The secondary outcome will be the global cognitive function assessed by the Repeatable Battery for the Assessment of Neuropsychological Status and event-related potential P300. Other outcomes will include specific cognitive domain (i.e. working memory), quality of life and social function. The results will be measured within 1 week before and after the intervention. Discussion: The results of this study will likely help find an economical and convenient rehabilitation method for the residual symptoms of schizophrenia and, at the same time, may promote the popularisation and application of traditional Chinese exercises and traditional Chinese medicine theories in the treatment of mental diseases. Trial registration: ClinicalTrials.gov registry number: NCT05310955.

Heterostructured Metal-Organic Frameworks/Polydopamine Coating Endows Polyetheretherketone Implants with Multimodal Osteogenicity and Photoswitchable Disinfection.

Clinically, bacteria-induced contagion and insufficient osseointegrative property inevitably elicit the failure of orthopedic implants. Herein, a heterostructured coating consisting of simvastatin (SIM)-laden metal-organic frameworks and polydopamine nanolayers is created on a porous bioinert polyetheretherketone implant. The heterostructured coating significantly promotes cytocompatibility and osteogenic differentiation through multimodal osteogenicity mechanisms of zinc ion (Zn2+ ) therapy, SIM drug therapy, and surface micro-/nano-topological stimulation. Under the illumination of near-infrared (NIR) light, singlet oxygen (1 O2 ) and local hyperthermia are produced; besides, NIR light dramatically accelerates the release of Zn2+ ions from heterostructured coatings. Gram-positive and -negative bacteria are effectively eradicated by the synergy of photothermal/photodynamic effects and photo-induced accelerated delivery of Zn2+ ions. The superior osteogenicity and osseointegration, as well as photoswitchable disinfection controlled by NIR light are corroborated via in vivo results. This work highlights the great potential of photoresponsive heterostructured orthopedic implants in treatment of the noninvasive bone reconstruction of bacteria-associated infectious tissues through multimodal phototherapy and photoswitchable ion-therapy.

Multi-activity cobalt ferrite/MXene nanoenzymes for drug-free phototherapy in bacterial infection treatment.

Drug-free antibacterial strategies are of great significance for pathogenic bacterial infection treatment in clinical practice. Phototherapy with antibacterial function plays a vital role in mainstream germicidal research. However, phototherapy could lead to residual heat and excess reactive oxygen species (ROS), which are the main side-effects during antibacterial treatment. Unique CoFe2O4/MXene (CM) nanoenzymes, which were fabricated with electrostatic interactions, have been designed to conquer those challenges caused by side-effects of phototherapy in our research. The CM nanoenzymes possess many promising properties including photothermal and photodynamic induced phototherapy and mimic peroxidase (POD), glutathione oxidase (GSHOx), and catalase (CAT). Upon treatment with near-infrared (NIR) light, CM nanoenzymes can create a local high-temperature circumstance as well as raise bacterial membrane permeability. Furthermore, the photodynamic process and multi-enzyme-mimicking activities of CM enzymes boost the interbacterial ROS level. Herein, bacteria can hardly survive in synergistic phototherapy and multi-enzyme-mimicking catalytic therapy in vitro and in vivo. Meanwhile, the CM nanoenzymes exhibit excellent biocompatibility in vitro and in vivo. Overall, this research establishes a strong foundation for effectively employing nanoenzymes, leading to a new way to cure bacterial infections.

Growth Factor-Decorated Ti3 C2 MXene/MoS2 2D Bio-Heterojunctions with Quad-Channel Photonic Disinfection for Effective Regeneration of Bacteria-Invaded Cutaneous Tissue.

Phototherapy has recently emerged as a competent alternative for combating bacterial infection without antibiotic-resistance risk. However, owing to the bacterial endogenous antioxidative glutathione (GSH), the exogenous reactive oxygen species (ROS) generated by phototherapy can hardly behave desired antibacterial effect. To address the daunting issue, a quad-channel synergistic antibacterial nano-platform of Ti3 C2 MXene/MoS2 (MM) 2D bio-heterojunctions (2D bio-HJs) are devised and fabricated, which possess photothermal, photodynamic, peroxidase-like (POD-like), and glutathione oxidase-like properties. Under near-infrared (NIR) laser exposure, the 2D bio-HJs both yield localized heating and raise extracellular ROS level, leading to bacterial inactivation. Synchronously, Mo4+ ions can easily invade into ruptured bacterial membrane, arouse intracellular ROS, and deplete intracellular GSH. Squeezed between the "ROS hurricane" from both internal and external sides, the bacteria are hugely slaughtered. After being further loaded with fibroblast growth factor-21 (FGF21), the 2D bio-HJs exhibit benign cytocompatibility and boost cell migration in vitro. Notably, the in vivo evaluations employing a mouse-infected wound model demonstrate the excellent photonic disinfection towards bacterial infection and accelerated wound healing. Overall, this work provides a powerful nano-platform for the effective regeneration of bacteria-invaded cutaneous tissue using 2D bio-HJs.

Two-dimensional nanocoating-enabled orthopedic implants for bimodal therapeutic applications.

As one of the promising orthopedic materials, polyetheretherketone (PEEK) has high chemical durability and similar mechanical properties to the cortical bone; nevertheless, the inherent bioinert nature of PEEK dramatically impedes its broader clinical applications in the management of bone infection. To address this challenge, herein, we developed a multifunctional two-dimensional (2D) nanocoating to assemble graphene oxide (GO) nanosheets, a polydopamine (pDA) nanofilm, and an oligopeptide onto the surface of porous sulfonated PEEK (SPEEK). The resulting multifunctional PEEK implants exhibited enhanced cytocompatibility, alkaline phosphatase activity, and calcium matrix deposition as well as osteogenesis-associated gene expression. Moreover, the animal experiments based on a rabbit femur defect model confirmed that the 2D nanocoating prominently boosted the in vivo osseointegration and bone remodeling. Besides, the GO/pDA hybrid complex anchoring on the SPEEK surface through π-π stacking can generate robust antibacterial phototherapy resulting from the synergetic photothermal/photodynamic therapeutic effects. Accordingly, this work provides a paradigm to empower inert PEEK implants with bi-/multi-modal therapeutic applications, such as against bone infection treatment.

HAp@GO drug delivery vehicle with dual-stimuli-triggered drug release property and efficient synergistic therapy function against cancer.

Nanoscale hydroxyapatite (HAp) is an optimal candidate material in biomedical area for its good biocompatibility and bioactivity. In this study, HAp nanorods are prepared via hydrothermal method and combined with monolayered graphene oxide (GO). The obtained HAp@GO with excellent biocompatibility is revealed to have high drug loading capacity (698.7 µg/mg) for anticancer drug doxorubicin (DOX) and efficient photothermal conversion property. And the drug release property of DOX loaded HAp@GO (HAp@GO-DOX) is demonstrated to be controlled by pH and near-infrared light, which is favorable for cancer therapy. in vitro studies on cancer therapy demonstrate that the combined treatment, compared with either chemotherapy or photothermal therapy alone, has better synergistic therapeutic effect. These findings prove the great potential application of the nanocomposites for cancer therapy.

Cobalt nanowire-based multifunctional platform for targeted chemo-photothermal synergistic cancer therapy.

Cobalt nanowires (CoNWs) simultaneously possessing advantages in photothermal effect, targeting drug delivery and photoacoustic imaging property are hopefully promising strategies to further improve the treatment efficiency and reduce the side effects of cancer chemotherapy. Herein, a unique cobalt-based structure decorated with graphene oxide (GO) and polyethylene glycol (PEG) is fabricated through a facile approach. The resultant nanohybrids show relatively low cytotoxicity, favorable biocompatibility as well as inherit the outstanding properties of cobalt. Moreover, CoNWs decorated with GO and PEG (CoNWs-GO-PEG) can load therapeutic drug molecules (e.g., doxorubicin, DOX) with a high drug loading capacity (992.91 mg/g), and simultaneously they are responsive to pH, NIR (near-infrared) irradiation and magnetism stimulation. Accordingly, CoNWs-GO-PEG-DOX shows the satisfactory effect of eliminating cancer cells with synergistic chemo-photothermal therapy in vitro. Current work provides a solid demonstration of the potential of CoNWs-GO-PEG for serving as a targeted antitumor agent in synergistic chemo-photothermal therapy.