The global crisis of antibiotic resistance has impelled the exigency to develop more effective drug delivery systems for the treatment of bacterial infection. The development of possessing high biocompatibility and targeted delivery of antimicrobials remains a persisting challenge. For programmable release of efficient antimicrobials in infection sites to enhance antibacterial activity, herein, we fabricated diselenide-bridged mesoporous organosilica nanoparticle-supported silver nanoparticles (Ag NPs) with high drug-loading capacity for the co-delivery of tobramycin (TOB) within one drug delivery system (Ag-MON@TOB (Se)). The resultant Ag-MON@TOB (Se) exhibited favorable biocompatibility due to its high stability in the physiological condition. Notably, such Ag-MON@TOB (Se) manifested a programmable structural destabilization to trigger sequential drug release in response to the oxidative stimuli within the bacterial infection microenvironment. In contradistinction to the oxidation-stable disulfide bond moieties within the framework of the nanocarrier (Ag-MON@TOB (S)), the Ag-MON@TOB (Se) with its programmed drug release behavior augmented prominent antibacterial therapy both in vitro and in vivo. This work represents a promising strategy for programmable drug release by harnessing a responsive degradable vehicle to enhance the treatment of bacterial infection.
Duck Tembusu virus (DTMUV) is an acute avian flavivirus that primarily infects poultry, mosquitoes, and some mammals including humans. The viral infection triggers reactive oxygen species (ROS) and inflammatory response that are crucial in mediating injury. Crafting multifunctional nanozymes that possess both ROS scavenging and anti-inflammatory activities presents formidable challenges. The study synthesized manganese dioxide cauliflowers (MnO2 Cfs) endowed with multiple enzyme-like activities (analogous to SOD, CAT, and GPX) that effectively alleviated the injury induced by DTMUV both in vitro and in vivo. Remarkably, MnO2 Cfs efficiently neutralized various ROS, encompassing hydrogen peroxide (H2O2), superoxide anion (O2·-) and hydroxyl radical (·OH). Our in vitro assessments showed that MnO2 Cfs could alleviate cytopathic effects and modulate the innate immune response during DTMUV infection through their ROS scavenging and anti-inflammatory properties. In vivo experiments supported these findings, demonstrating that ducklings therapied by MnO2 Cfs experienced alleviated injury during DTMUV infection. Importantly, MnO2 Cfs also effectively inhibited DTMUV replication in both laboratory and field conditions. This study presents a novel strategy for nanozyme design, promising significant therapeutic potential for treating viral inflammatory diseases.
Minimally invasive methods for detecting glucose, cholesterol and hydrogen peroxide are crucial for monitoring the nutritional and health status of humans and animals. The peroxidase mimetic activity by nanozymes is one of the versatile methods for detecting glucose, cholesterol, hydrogen peroxide, and other biomolecules. However, the strict requirement of acidic pH limits their sensing and interfacing ability with natural enzymes. The present study developed bovine serum albumin (BSA) coated gold nanoclusters (AuNC) immobilized on paper fabric to enable single-step visual detection of glucose, cholesterol and hydrogen peroxide in complex biological fluids like serum and milk. The BSA-AuNC suspension and immobilized paper fabric synergistically interface with the natural oxidative enzymes, glucose oxidase or cholesterol oxidase, at physiological pH. The concomitant loss in the fluorescent intensity of BSA-AuNC-loaded paper fabric exposed to the generated hydrogen peroxide (glucose/glucose oxidase or cholesterol/cholesterol oxidase) was directly proportional to the concentration of glucose or cholesterol. These reactions enabled simple visual detection as well as quantification of hydrogen peroxide, glucose and cholesterol using Image-J software and common smartphone-based mobile applications. The detection ability of BSA-AuNC-embedded paper fabric is specific and remains unaltered in the presence of similar oxidase enzymes or similar substrate analogues. With these unique features, the BSA-AuNC embedded paper fabric stands out as a prominent analytical device with enormous potential as a simple, user-friendly detection tool for monitoring biomolecules that are important to health, nutrition, and environmental safeguarding.
Two-photon photodynamic therapy (TP-PDT) offers an innovative approach to cancer treatment that utilizes near-infrared light to activate photosensitizers and generate reactive oxygen species (ROS) for targeted cancer cell elimination. TiO2-CUR-Sofast (TCS), which uses TiO2 nanoparticles and Sofast cationic polymer to modify curcumin (CUR), has demonstrated potential as a photosensitizer under visible light irradiation, addressing the limitations of CUR's narrow spectral range and low bioavailability. This study explores the utility of the two-photon technique to activate TCS within the infrared spectrum, aiming to enhance ROS production and penetration depth compared to traditional CUR. TCS exhibits a significantly higher ROS production at 900 nm excitation wavelength, approximately 6-7 times that of CUR, signifying a substantial increase in efficiency. In TP-PDT, TCS showed significant phototoxicity against HeLa and T24 cell lines compared to CUR. Furthermore, TCS's photodynamic efficacy is further confirmed by cell apoptosis and necrosis studies, where approximately 89 % of cells treated with TCS under 900 nm light irradiation were observed in an apoptosis/necrosis state. And the TP-PDT effect in deep tissue was simulated using pig skin. It shows that the two-photon excitation has a significant penetration depth advantage over the single-photon excitation. These results indicate that the two-photon PDT scheme of TCS has greater potential than the single-photon PDT scheme in the treatment of cancer, and provides an experimental foundation for the effective treatment of deep lesions.