An Acceptor-Donor-Acceptor Structured Nano-Aggregate for NIR-Triggered Interventional Photoimmunotherapy of Cervical Cancer.

Compared with conventional therapies, photoimmunotherapy offers precise targeted cancer treatment with minimal damage to healthy tissues and reduced side effects, but its efficacy may be limited by shallow light penetration and the potential for tumor resistance. Here, an acceptor-donor-acceptor (A-D-A)-structured nanoaggregate is developed with dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), triggered by single near-infrared (NIR) light. Benefiting from strong intramolecular charge transfer (ICT), the A-D-A-structured nanoaggregates exhibit broad absorption extending to the NIR region and effectively suppressed fluorescence, which enables deep penetration and efficient photothermal conversion (η = 67.94%). A suitable HOMO-LUMO distribution facilitates sufficient intersystem crossing (ISC) to convert ground-state oxygen (3O2) to singlet oxygen (1O2) and superoxide anions (·O2 -), and catalyze hydroxyl radical (·OH) generation. The enhanced ICT and ISC effects endow the A-D-A structured nanoaggregates with efficient PTT and PDT for cervical cancer, inducing efficient immunogenic cell death. In combination with clinical aluminum adjuvant gel, a novel photoimmunotherapy strategy for cervical cancer is developed and demonstrated to significantly inhibit primary and metastatic tumors in orthotopic and intraperitoneal metastasis cervical cancer animal models. The noninvasive therapy strategy offers new insights for clinical early-stage and advanced cervical cancer treatment.

Oral Heterojunction Coupling Interventional Optical Fiber Mediates Synergistic Therapy for Orthotopic Rectal Cancer.

Catalytic therapy has shown great potential for clinical application. However, conventional catalytic therapies rely on reactive oxygen species (ROS) as "therapeutic drugs," which have limitations in effectively inhibiting tumor recurrence and metastasis. Here, a biomimetic heterojunction catalyst is developed that can actively target orthotopic rectal cancer after oral administration. The heterojunction catalyst is composed of quatrefoil star-shaped BiVO4 (BVO) and ZnIn2S4 (ZIS) nanosheets through an in situ direct growth technique. Poly-norepinephrine and macrophage membrane coatings afford the biomimetic heterojunction catalyst (BVO/ZIS@M), which has high rectal cancer targeting and retention abilities. The coupled optical fiber intervention technology activates the multicenter coordination of five catalytic reactions of heterojunction catalysts, including two reduction reactions (O2→·O2 - and CO2→CO) and three oxidation reactions (H2O→·OH, GSH→GSSG, and LA→PA). These catalytic reactions not only induce immunogenic death in tumor cells through the efficient generation of ROS/CO and the consumption of GSH but also specifically lead to the use of lactic acid (LA) as an electron donor to improve catalytic activity and disrupt the LA-mediated immunosuppressive microenvironment, mediating synergistic catalysis and immunotherapy for orthotopic rectal cancer. Therefore, this optical fiber intervention triggered the combination of heterojunction catalytic therapy and immunotherapy, which exhibits prominent antitumor effects.

Multifunctional Bioactive Nanozyme Systems for Enhanced Diabetic Wound Healing.

The protracted transition from inflammation to proliferation in diabetic wound healing poses significant challenges, exacerbated by persistent inflammatory responses and inadequate vascularization. To address these issues, a novel nanozymatic therapeutic approach utilizing asymmetrically structured MnO2-Au-mSiO2@aFGF Janus nanoparticles is engineered. Nanozymes featuring a mSiO2 head and MnO2 extensions, into which acidic fibroblast growth factor (aFGF) is encapsulated, resulting in MnO2-Au-mSiO2@aFGF Janus nanoparticles (mSAM@aFGF), are synthesized. This nanozyme system effectively emulates enzymatic activities of catalase (CAT) and superoxide dismutase (SOD), catalyzing degradation of reactive oxygen species (ROS) and generating oxygen. In addition, controlled release of aFGF fosters tissue regeneration and vascularization. In vitro studies demonstrate that mSAM@aFGF significantly alleviates oxidative stress in cells, and enhances cell proliferation, migration, and angiogenesis. An injectable hydrogel based on photocrosslinked hyaluronic acid (HAMA), incorporating the nanozymatic ROS-scavenging and growth factor-releasing system, is developed. The HAMA-mSAM@aFGF hydrogel exhibits multifaceted benefits in a diabetic wound model, including injectability, wound adhesion, hemostasis, anti-inflammatory effects, macrophage polarization from M1 to M2 phenotype, and promotion of vascularization. These attributes underscore the potential of this system to facilitate transition from chronic inflammation to the proliferative phase of wound repair, offering a promising therapeutic strategy for diabetic wound management.

Functional modification of gut bacteria for disease diagnosis and treatment.

Intestinal bacteria help keep humans healthy by regulating lipid and glucose metabolism as well as the immunological and neurological systems. Oral treatment using intestinal bacteria is limited by the high acidity of stomach fluids and the immune system's attack on foreign bacteria. Scientists have created coatings and workarounds to overcome these limitations and improve bacterial therapy. These preparations have demonstrated promising outcomes, with advances in synthetic biology and optogenetics improving their focused colonization and controlled release. Engineering bacteria preparations have become a revolutionary therapeutic approach that converts intestinal bacteria into cellular factories for medicinal chemical synthesis. The present paper discusses various aspects of engineering bacteria preparations, including wrapping materials, biomedical uses, and future developments.

Bifunctional black phosphorus quantum dots platform: Delivery and remarkable immunotherapy enhancement of STING agonist.

Cancer immunotherapy has been developed to improve therapeutic effects for patients by activating the innate immune stimulator of interferon gene (STING) pathway. However, most patients cannot benefit from this therapy, mainly due to the problems of excessively low immune responses and lack of tumor specificity. Herein, we report a solution to these two problems by developing a bifunctional platform of black phosphorus quantum dots (BPQDs) for STING agonists. Specifically, BPQDs could connect targeted functional groups and regulate surface zeta potential by coordinating metal ions to increase loading (over 5 times) while maintaining high universality (7 STING agonists). The controlled release of STING agonists enabled specific interactions with their proteins, activating the STING pathway and stimulating the secretion release of immunosuppressive factors by phosphorylating TBK1 and IFN-IRF3 and secreting high levels of immunostimulatory cytokines, including IL-6, IFN-α, and IFN-ß. Moreover, the immunotherapy was enhanced was enhanced mild photothermal therapy (PTT) of BPQDs platform, producing enough T cells to eliminate tumors and prevent tumor recurrence. This work facilitates further research on targeted delivery of small-molecule immune drugs to enhance the development of clinical immunotherapy.

Biomimetic piezoelectric nanomaterial-modified oral microrobots for targeted catalytic and immunotherapy of colorectal cancer.

Lactic acid (LA) accumulation in the tumor microenvironment poses notable challenges to effective tumor immunotherapy. Here, an intelligent tumor treatment microrobot based on the unique physiological structure and metabolic characteristics of Veillonella atypica (VA) is proposed by loading Staphylococcus aureus cell membrane-coating BaTiO3 nanocubes (SAM@BTO) on the surface of VA cells (VA-SAM@BTO) via click chemical reaction. Following oral administration, VA-SAM@BTO accurately targeted orthotopic colorectal cancer through inflammatory targeting of SAM and hypoxic targeting of VA. Under in vitro ultrasonic stimulation, BTO catalyzed two reduction reactions (O2 → •O2- and CO2 → CO) and three oxidation reactions (H2O → •OH, GSH → GSSG, and LA → PA) simultaneously, effectively inducing immunogenic death of tumor cells. BTO catalyzed the oxidative coupling of VA cells metabolized LA, effectively disrupting the immunosuppressive microenvironment, improving dendritic cell maturation and macrophage M1 polarization, and increasing effector T cell proportions while decreasing regulatory T cell numbers, which facilitates synergetic catalysis and immunotherapy.

Data-Physics Fusion-Driven Defect Predictions for Titanium Alloy Casing Using Neural Network.

The quality of Ti alloy casing is crucial for the safe and stable operation of aero engines. However, the fluctuation of key process parameters during the investment casting process of titanium alloy casings has a significant influence on the volume and number of porosity defects, and this influence cannot be effectively suppressed at present. Therefore, this paper proposes a strategy to control the influence of process parameters on shrinkage volume and number. This study constructed multiple regression prediction models and neural network prediction models of porosity volume and number for a ZTC4 casing by simulating the gravity investment casting process. The results show that the multiple regression prediction model and neural network prediction model of shrinkage cavity total volume have an accuracy of over 99%. The accuracy of the neural network prediction model is higher than that of the multiple regression model, and the neural network model realizes the accurate prediction of shrinkage defect volume and defect number through pouring temperature, pouring time, and mold shell temperature. The sensitivity degree of casing defects to key process parameters, from high to low, is as follows: pouring temperature, pouring time, and mold temperature. Further optimizing the key process parameter window reduces the influence of process parameter fluctuation on the volume and number of porosity defects in casing castings. This study provides a reference for actual production control process parameters to reduce shrinkage cavity and loose defects.

Improvements in Wear and Corrosion Resistance of Ti-W-Alloyed Gray Cast Iron by Tailoring Its Microstructural Properties.

The improved wear and corrosion resistance of gray cast iron (GCI) with enhanced mechanical properties is a proven stepping stone towards the longevity of its versatile industrial applications. In this article, we have tailored the microstructural properties of GCI by alloying it with titanium (Ti) and tungsten (W) additives, which resulted in improved mechanical, wear, and corrosion resistance. The results also show the nucleation of the B-, D-, and E-type graphite flakes with the A-type graphite flake in the alloyed GCI microstructure. Additionally, the alloyed microstructure demonstrated that the ratio of the pearlite volume percentage to the ferrite volume percentage was improved from 67/33 to 87/13, whereas a reduction in the maximum graphite length and average grain size from 356 ± 31 µm to 297 ± 16 µm and 378 ± 18 µm to 349 ± 19 µm was detected. Consequently, it improved the mechanical properties and wear and corrosion resistance of alloyed GCI. A significant improvement in Brinell hardness, yield strength, and tensile strength of the modified microstructure from 213 ± 7 BHN to 272 ± 8 BHN, 260 ± 3 MPa to 310 ± 2 MPa, and 346 ± 12 MPa to 375 ± 7 MPa was achieved, respectively. The substantial reduction in the wear rate of alloyed GCI from 8.49 × 10-3 mm3/N.m to 1.59 × 10-3 mm3/N.m resulted in the upgradation of the surface roughness quality from 297.625 nm to 192.553 nm. Due to the increase in the corrosion potential from -0.5832 V to -0.4813 V, the impedance of the alloyed GCI was increased from 1545 Ohm·cm2 to 2290 Ohm·cm2. On the basis of the achieved experimental results, it is suggested that the reliability of alloyed GCI based on experimentally validated microstructural compositions can be ensured during the operation of plants and components in a severe wear and corrosive environment. It can be predicted that the proposed alloyed GCI components are capable of preventing the premature failure of high-tech components susceptible to a wear and corrosion environment.

Unzippable Siamese Nanoparticles for Programmed Two-Stage Cancer Immunotherapy.

Epigenetic drugs (epi-drugs) can destruct cancer cells and initiate both innate and adaptive immunity, yet they have achieved very limited success in solid tumors so far, partly attributing to their concurrent induction of the myeloid-derived suppressor cell (MDSC) population. Here, dissociable Siamese nanoparticles (SIANPs) are developed for tumor cell-targeted delivery of epi-drug CM-272 and MDSC-targeted delivery of small molecule inhibitor Ibrutinib. The SIANPs are assembled via interparticle DNA annealing and detached via tumor microenvironment-triggered strand separation. Such binary regulation induces endogenous retrovirus expression and immunogenic cell death in tumor cells while restraining the immunosuppressive effects of MDSCs, and synergistically promotes dendritic cell maturation and CD8+ T cell activation for tumor inhibition. Significantly, immune microenvironment remodeling via SIANPs further overcomes tumor resistance to immune checkpoint blockade therapy. This study represents a two-pronged approach for orchestrating immune responses, and paves a new way for employing epi-drugs in cancer immunotherapy.

Dismantlable Coronated Nanoparticles for Coupling the Induction and Perception of Immunogenic Cell Death.

Therapy-induced immunogenic cell death (ICD) can initiate both innate and adaptive immune responses for amplified anti-tumor efficacy. However, dying cell-released ICD signals are prone to being sequestered by the TIM-3 receptors on dendritic cell (DC) surfaces, preventing immune surveillance. Herein, dismantlable coronated nanoparticles (NPs) are fabricated as a type of spatiotemporally controlled nanocarriers for coupling tumor cell-mediated ICD induction to DC-mediated immune sensing. These NPs are loaded with an ICD inducer, mitoxantrone (MTO), and wrapped by a redox-labile anti-TIM-3 (αTIM-3) antibody corona, forming a separable core-shell structure. The antibody corona disintegrates under high levels of extracellular reactive oxygen species in the tumor microenvironment, exposing the MTO-loaded NP core for ICD induction and releasing functional αTIM-3 molecules for DC sensitization. Systemic administration of the coronated NPs augments DC maturation, promotes cytotoxic T cell recruitment, enhances tumor susceptibility to immune checkpoint blockade, and prevents the side effects of MTO. This study develops a promising nanoplatform to unleash the potential of host immunity in cancer therapy.

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.

Programmed microalgae-gel promotes chronic wound healing in diabetes.

Chronic diabetic wounds are at lifelong risk of developing diabetic foot ulcers owing to severe hypoxia, excessive reactive oxygen species (ROS), a complex inflammatory microenvironment, and the potential for bacterial infection. Here we develop a programmed treatment strategy employing live Haematococcus (HEA). By modulating light intensity, HEA can be programmed to perform a variety of functions, such as antibacterial activity, oxygen supply, ROS scavenging, and immune regulation, suggesting its potential for use in programmed therapy. Under high light intensity (658 nm, 0.5 W/cm2), green HEA (GHEA) with efficient photothermal conversion mediate wound surface disinfection. By decreasing the light intensity (658 nm, 0.1 W/cm2), the photosynthetic system of GHEA can continuously produce oxygen, effectively resolving the problems of hypoxia and promoting vascular regeneration. Continuous light irradiation induces astaxanthin (AST) accumulation in HEA cells, resulting in a gradual transformation from a green to red hue (RHEA). RHEA effectively scavenges excess ROS, enhances the expression of intracellular antioxidant enzymes, and directs polarization to M2 macrophages by secreting AST vesicles via exosomes. The living HEA hydrogel can sterilize and enhance cell proliferation and migration and promote neoangiogenesis, which could improve infected diabetic wound healing in female mice.

Platelet-derived drug delivery systems: Pioneering treatment for cancer, cardiovascular diseases, infectious diseases, and beyond.

Platelets play a critical role as circulating cells in the human body and contribute to essential physiological processes such as blood clotting, hemostasis, vascular repair, and thrombus formation. Currently, platelets are extensively employed in the development of innovative biomimetic drug delivery systems, offering significant enhancements in circulation time, biocompatibility, and targeted delivery efficiency compared to conventional drug delivery approaches. Leveraging the unique physiological functions of platelets, these platelet-derived drug delivery systems (DDSs) hold great promise for the treatment of diverse diseases, including cancer, cardiovascular diseases, infectious diseases, wound healing and other diseases. This review primarily focuses on the design and characteristics of existing platelet-derived DDSs, including their preparation and characterization methods. Furthermore, this review comprehensively outlines the applications of these materials across various diseases, offering a holistic understanding of their therapeutic potential. This study aimed to provide a comprehensive overview of the potential value of these materials in clinical treatment, serving as a valuable reference for the advancement of novel platelet-derived DDSs and their broader utilization in the field of disease treatment.