Xijian Liu

The diabetic‐infected wound microenvironment, marked by elevated reactive oxygen species (ROS) levels, ongoing inflammation, and defective angiogenesis, interferes with the normal wound healing cascade and contributes to delayed and treatment‐resistant repair. However, most existing wound dressings lack the capability to dynamically adapt to these spatiotemporally evolving conditions. Herein, a smart and microenvironment‐programmable PVH‐ST hydrogel is developed to achieve phased and spatiotemporally coordinated regulation of diabetic‐infected wound healing. The hydrogel is engineered by integrating strontium (Sr)‐tannic acid (ST) nanoparticles into a polyvinyl alcohol (PVA) and hyaluronic acid (HA) matrix through a boric acid‐mediated multilevel dynamic crosslinking network, endowing the system with mechanical robustness suitable for daily motion. Upon wound occurrence, the PVH‐ST hydrogel rapidly induces hemostasis and establishes a bioactive provisional matrix. In response to the ROS‐enriched infected microenvironment, the dynamic borate bonds undergo on‐demand dissociation, triggering controlled release of ST nanoparticles. Released ST nanoparticles integrate antibacterial and antioxidant functions and reduce inflammatory burden via modulation of NF‐κB signaling and skewing macrophages toward an M2 pro‐regenerative state. Concurrently, the sustained release of Sr ²⁺ ions activates VEGF‐associated angiogenic signaling and epithelialization pathways, thereby promoting vascularization and epithelial reconstruction for diabetic‐infected wounds.

Bone infections associated with the formation of intracellular bacterial niches in macrophages and bone cells play an important role in the long-lasting nature of chronic infections. One major mechanism of intracellular bacterial persistence lies in the low antibiotic permeability and subverted immune responses. It is now increasingly apparent that metal elements such as Mn, Zn, and Se exploit the stimulator of interferon genes (STING) pathway in immune cells to combat invading pathogens and intrinsic aberrant cells. Here, we report a prototype of bacterial metalloimmunotherapy using a synthetic inorganic STING sensitizer (SSZ), which comprises Se-loaded mesoporous silica nanoparticles and ZnO quantum dot lids. Mechanistically, the inorganic STING sensitizer could restore the bactericidal activity of lysosomes in macrophages and generate type I interferons, achieving effective intracellular bacterial clearance. Topical application of the inorganic STING sensitizer initiated robust antibacterial immunity, leading to obvious therapeutic efficacy toward both intracellular bacteria and biofilms in a mouse osteomyelitis model. Rechallenging the SSZ-cured mice with bacteria led to effective inhibition of bacterial growth, suggesting the generation of long-term antibacterial memory responses. This antibacterial strategy was also proven effective in a rabbit knee prosthetic infection model. Overall, the inorganic STING sensitizer offers an alternative approach for intracellular bacterial treatments, and this underscores the great potential of metalloimmunotherapy for infectious diseases.

A pH-responsive hydrogel nanocomposite (MCAG-Gel) was designed for postoperative glioma treatment, which exhibited high biosafety and significant anti-tumor performance through chemotherapy/enzymatic therapy.

Benign prostatic hyperplasia (BPH) presents a significant clinical challenge, with conventional therapies carrying substantial risks, including urinary retention, sexual dysfunction, and prolonged recovery. To address the urgent need for safer, ultra-minimally invasive alternatives, we developed a sonosensitizing nanoplatform using copper-manganese-doped mesoporous silica nanoparticles (Cu-Mn@SiO₂) for ultrasound-induced sonodynamic therapy (SDT). Here, we demonstrate that this innovative strategy provides highly effective and precisely targeted therapy for BPH. In vitro studies revealed that Cu-Mn@SiO₂-mediated SDT significantly amplified intracellular reactive oxygen species (ROS) generation, triggering oxeiptosis characterized by PGAM5 cleavage, mitochondrial membrane depolarization, and mitochondrial damage in both BPH-1 epithelial and WPMY-1 stromal cells. In a testosterone-induced BPH rat model, a Cu-Mn@SiO₂-combined, localized SDT treatment resulted in a substantial 60% reduction in prostatic weight and a marked improvement in urinary function. Thermal imaging confirmed prostate-specific hyperthermia without affecting the surrounding tissues. Histopathology revealed reduced collagen deposition and restored glandular morphology with comprehensive biosafety assessments showing no systemic toxicity. By precisely inducing localized oxeiptosis within hyperplastic prostatic tissue via focused ultrasound activation, this Cu-Mn@SiO₂-based nanoplatform represents a clinically translatable, ultra-minimally invasive therapeutic strategy offering a superior safety profile for BPH management.

Non‐targeted chemotherapy remains the primary therapeutic approach for treating triple‐negative breast cancer (TNBC), but it frequently results in multidrug resistance and severe side effects. In this study, a responsive biodegradable zinc‐doped MoS_2‐x nanosheet is developed with rich sulfide vacancies (ZMS) to enhance sono‐chemotherapy in TNBC by simultaneously inhibiting multidrug resistance through triple‐pathway modulation (reactive oxygen species, H₂S, and Zn²⁺). The introduction of sulfide‐vacancies via Zn doping significantly inhibits electron‐hole recombination, and eventually boosts the generation of reactive oxygen species under ultrasound (US) activation to enhance sonodynamic therapy (SDT). In addition, the ZMS/DOX can degrade in an acidic tumor microenvironment (TME) to release DOX (doxorubicin hydrochloride), Zn²⁺, and H₂S. Zn²⁺ inhibits intracellular ATP production by disrupting glycolysis in cancer cells, while H₂S synergistically reduces intracellular ATP levels by impairing the mitochondrial electron transport chain. Furthermore, the reduction in ATP levels suppresses the expression of P‐glycoprotein, thereby overcoming drug resistance. Additionally, ZMS exhibits catalase‐like activity to convert H₂O₂ into O₂ in TME, relieving the tumor's hypoxia as well as enhancing the therapeutic efficacy of SDT and chemotherapy. The proposed biodegradable therapeutic platform holds great promise for strengthening sono‐chemotherapy in TNBC treatment and overcoming the limitations associated with traditional chemotherapy.

Purpose: Myocardial ischemia-reperfusion (IR) injury, a significant challenge in cardiovascular treatment, is primarily driven by ferroptosis and mitochondrial dysfunction. Despite extensive research, no clinical therapies effectively target ferroptosis in IR injury. This study aims to develop selenium-quantum-dot-loaded porous silica nanospheres (Se@PSN) as a novel therapeutic approach to address IR injury. Patients and Methods: Se@PSN were synthesized and tested for their reactive oxygen species (ROS) scavenging capabilities and biocompatibility. Additionally, the effects of Se@PSN on ferroptosis, mitochondrial damage, oxidative stress, and myocardial IR injury severity were evaluated. Results: Se@PSN enhanced the stability of selenium quantum dots and exhibited strong ROS scavenging abilities. Additionally, Se@PSN exhibited excellent biocompatibility. The Se@PSN treatment increased GPX4 levels, effectively inhibiting ferroptosis in cardiomyocytes. Furthermore, Se@PSN promoted the expression of mitochondrial respiratory complexes, mitigating oxidative phosphorylation damage and preserving mitochondrial function. These effects collectively resulted in reduced myocardial loss, inflammation, and fibrosis following IR injury. Compared to PSN alone, Se@PSN showed superior therapeutic efficacy against IR injury. Conclusion: Se@PSN exhibit great potential in reducing ferroptosis and protecting mitochondrial function, making them a promising therapeutic approach for the treatment of myocardial IR injury.

Neuromuscular abnormality is the leading cause of disability in adults. Understanding the complex interplay between muscle structure and function is crucial for effective treatment and rehabilitation. However, the substantial deformation of muscles during movement (up to 40%) poses challenges for accurate assessment. To address this, we developed a wearable structural-functional sensing patch (WSFP) that enables synchronous analysis of muscle structure and function. The WSFP incorporates a soft, stretchable electrode array for high-performance electrophysiological monitoring with low contact impedance and high stability. Its innovative design absorbs skin deformation stress, ensuring stable adhesion of a flexible ultrasound transducer array, offering higher-fidelity imaging. With dynamic tissue imaging, it allows real-time visualization of muscle structure. The WSFP achieves superior accuracy in dynamic action recognition and disease assessment compared to single-modal methods, maintaining stable operation during motion for up to 72 hours. This study advances neuromuscular system analysis and improves diagnostic precision.