Mitigating Lactate-Associated Immunosuppression against Intracellular Bacteria Using Thermoresponsive Nanoparticles for Septic Arthritis Therapy

Intracellular bacteria are the major contributor to the intractability of septic arthritis, which are sequestered in macrophages to undermine the innate immune response and avoid the antibacterial effect of antibiotics due to the obstruction of the cell membrane. Herein, we report a thermoresponsive nanoparticle, which consists of a phase-change material shell (fatty acids) and an oxygen-producing core (CaO2–vancomycin). Under external thermal stimulation, the shell of the nanoparticle transforms from a solid phase to a liquid phase. Then the CaO2–Vancomycin core is exposed to the surrounding aqueous solution to release vancomycin and generate Ca(OH)2 and oxygen, thereby depleting accumulated lactate to mitigate lactate-associated immunosuppression, stabilizing hypoxia-inducible factor-1α (HIF-1α) to enhance M1-like polarization of macrophages, and increasing reactive oxygen species (ROS) and reactive nitrogen species (RNS) production. This combined effect between the controlled release of antibiotics and enhancement of host innate immunity provides a promising strategy to combat intracellular bacteria for septic arthritis therapy

Alginate Hydrogel-Embedded Capillary Sensor for Quantitative Immunoassay with Naked Eye

We have developed an alginate hydrogel-embedded capillary sensor (AHCS) for naked eye-based quantification of immunoassay. Alkaline phosphatase (ALP) can modulate gel-sol transformation to increase the permeability of Cu2+-cross-linked alginate hydrogel film in the AHCS, followed by solution exchange into the capillary. Through measuring the length of the liquid phase of the microfluidics in the capillary at a given time, the concentration of the ALP could be quantified with the naked eye. Since ALP is widely applied as a signal reporter for immunoassays, the AHCS could easily accommodate conventional immune sensing platforms. We justify the practicality of AHCS with hepatitis B virus surface antigen (HBsAg) in serum samples and got comparable results with commercialized immunoassay. This AHCS is easy to make and use, effective in cost, and robust in quantification with the naked eye, showing great promise for next generation point-of-care testing

Glucose-driven transformable complex eliminates biofilm and alleviates inflamm-aging for diabetic periodontitis therapy

Diabetic periodontitis is a major complication of diabetes, which has a deep involvement in teeth loss and more serious systematic diseases, including Alzheimer's disease, atherosclerosis and cancers. Diabetic periodontitis is difficult to treat because of recalcitrant infection and hyperglycemia-induced tissue dysfunction. Current treatments fail to completely eliminate infection due to the diffusion-reaction inhibition of biofilm, and ignore the tissue dysfunction. Here, we design a glucose-driven transformable complex, composed of calcium alginate (CaAlg) hydrogel shell and Zeolitic imidazolate framework-8 (ZIF-8) core encapsulating Glucose oxidase (GOx)/Catalase (CAT) and Minocycline (MINO), named as CaAlg@MINO/GOx/CAT/ZIF-8 (CMGCZ). The reaction product of glucose-scavenging, gluconic acid, could dissolve ZIF-8 core and transform CMGCZ from inflexible to flexible, facilitating the complex to overcome the diffusion-reaction inhibition of biofilm. Meanwhile, reduced glucose concentration could ameliorate the pyroptosis of macrophages to decrease the secretion of pro-inflammatory factors, thereby reducing inflamm-aging to alleviate periodontal dysfunction

Bright AIE Nanoparticles for Two-Photon Imaging and Localized Compound Therapy of Cancers.pdf

Photodynamic therapy (PDT) is a non-invasive therapeutic strategy for cancer treatment but it always suffers from low reactive oxygen species (ROS) efficiency generated from traditional organic dyes owing to weak absorption in the optical transparent window of biological tissues and fluorescence quenching at a concentrated solution or in nanoparticles. Herein, we present cationic lipid-encapsulated aggregation-induced emission (AIE) nanoparticles (NPs) that have a high quantum yield (23%) and a maximum two-photon absorption (TPA) cross-section of 560 GM irradiated by near infrared light (800 nm). The AIE NPs can serve as imaging agents for spatiotemporal imaging of tumor tissues with a penetration depth up to 505 µm on mice melanoma model. Noteworthy, the AIE NPs can efficiently generate singlet oxygen (1O2) and highly toxic hydroxyl radicals (·OH) upon 800 nm-light irradiation for photodynamic tumor ablation. In addition, the AIE NPs can be effectively cleared from the mouse body after the imaging and therapy. This study provides a new strategy to develop theranostic agent for cancer image-guided PDT with high brightness, superior photostability and high biosafet