Apoptotic bodies encapsulating Ti2N nanosheets for synergistic chemo-photothermal therapy.

Extracellular vesicles (EVs) have great potential in oncology drug delivery because of their unique biological origin. Apoptotic bodies (ABs), as a member of the EV family, offer distinct advantages in terms of size, availability and membrane properties, but have been neglected for a long time. Here, using ABs and Ti2N nanosheets, we propose a novel drug delivery system (Ti2N-DOX@ABs), which exhibit a homologous targeting ability for dual-strategy tumor therapy with intrinsic biological property. The experimental results demonstrate that such a drug delivery system possesses a drug loading capacity of 496.5% and a near-infrared photothermal conversion efficiency of 38.4%. In addition, the investigation of drug internalization process proved that Ti2N-DOX@ABs featured a supreme biocompatibility. Finally, the dual-strategy response based on photothermal and chemotherapeutic effects was studied under near-infrared laser radiation. This work explores the opportunity of apoptosome membranes in nanomedicine systems, which provides a technical reference for cancer-oriented precision medicine research.

A H2S-Evolving Alternately-Catalytic Enzyme Bio-Heterojunction with Antibacterial and Macrophage-Reprogramming Activity for All-Stage Infectious Wound Regeneration.

The disorder of the macrophage phenotype and the hostile by-product of lactate evoked by pathogenic infection in hypoxic deep wound inevitably lead to the stagnant skin regeneration. In this study, hydrogen sulfide (H2S)-evolving alternately catalytic bio-heterojunction enzyme (AC-BioHJzyme) consisting of CuFe2S3 and lactate oxidase (LOD) named as CuFe2S3@LOD is developed. AC-BioHJzyme exhibits circular enzyme-mimetic antibacterial (EMA) activity and macrophage re-rousing capability, which can be activated by near-infrared-II (NIR-II) light. In this system, LOD exhausts lactate derived from bacterial anaerobic respiration and generated hydrogen peroxide (H2O2), which provides an abundant stock for the peroxidase-mimetic activity to convert the produced H2O2 into germicidal •OH. The GPx-mimetic activity endows AC-BioHJzyme with a glutathione consumption property to block the antioxidant systems in bacterial metabolism, while the O2 provided by the CAT-mimetic activity can generate 1O2 under the NIR-II irradiation. Synchronously, the H2S gas liberated from CuFe2S3@LOD under the infectious micromilieu allows the reduction of Fe(III)/Cu(II) to Fe(II)/Cu(І), resulting in sustained circular EMA activity. In vitro and in vivo assays indicate that the CuFe2S3@LOD AC-BioHJzyme significantly facilitates the infectious cutaneous regeneration by killing bacteria, facilitating epithelialization/collagen deposition, promoting angiogenesis, and reprogramming macrophages. This study provides a countermeasure for deep infectious wound healing via circular enzyme-mimetic antibiosis and macrophage re-rousing.

A SERS-assisted 3D organotypic microfluidic chip for in-situ visualization and monitoring breast cancer extravasation process.

Extravasation, as one of the key steps in cancer metastasis, refers to the process where tumor cells escape the bloodstream by crossing the vascular endothelium and invade the targeted tissue, which accounts for the low five-year survival rate of cancer patients. Understanding the mechanism of cancer metastasis and inhibiting extravasation are crucial to improve patient prognosis. Here, a 3D organotypic microfluidic chip combined with SERS-based protein imprinted nanomaterials (SPINs) was proposed to study the extravasation process in vitro. The chip consists of a collagen gel channel and a vascular channel where human vein endothelial cells (HUVECs) and breast cancer cells are injected sequentially to induce extravasation. By comparing two subtypes of breast cancer cells (MCF-7 and MDA-MB-231), we successfully observed the difference in extravasation capabilities between two kinds of cells through fluorescence imaging. Meanwhile, thanks to the high specificity of molecular imprinting technology and the high sensitivity of surface enhanced Raman scattering (SERS), SPINs were utilized to analyze the concentration of several cancer secretions (interleukin-6 and interleukin-8) in complex biological fluid in real-time. Further, our model showed that downregulation of secretions by therapeutic drugs can inhibit the extravasation of breast cancers. This microfluidic model may pave the way for the fundamental research of the cancer metastasis and evaluating the therapeutic efficacy of potential drugs.

Multi-Functional Bio-HJzyme: Revolutionizing Diabetic Skin Regeneration with its Glucose-Unlocked Sterilization and Programmed Anti-Inflammatory Effects.

Antibacterial dynamic therapy (ADT) triggered by reactive oxygen species (ROS) is promising for diabetic infectious disease treatment. However, the limited local O2 /H2 O2 production and post-treatment inflammation remain long-standing issues. To address these challenges, a novel H2 -evolving bio-heterojunction enzyme (Bio-HJzyme) consisting of graphite-phase carbon nitride/copper sulfide (CN/Cu2-x S) heterojunction and glucose oxidase (GOx) is created. The Bio-HJzyme offers glutathione peroxidase (GPx), peroxidase (POD), and catalase (CAT) mimetic activities; provides anti-pathogen properties via programmed light activation; and effectively promotes diabetic wound healing. Specifically, its GPx-mimetic activity and the presence of GOx significantly enhance the yield of H2 O2 , which can be catalyzed through POD-mimetic activity to produce highly germicidal •OH. The H2 O2 can also be catalyzed to H2 O and O2 , assisted by the CAT-mimetic activity. The catalyzed products can then be catalyzed into germicidal •OH and •O2 - under NIR light irradiation, giving enhanced ADT. Further, CN can split water to form H2 under solar light, which dramatically suppresses the inflammation caused by excessive ROS. In vivo evaluation confirms that Bio-HJzyme promotes the regeneration of diabetic infectious skin through killing bacteria, enhancing angiogenesis, promoting wound bed epithelialization, and reinforcing anti-inflammatory responses; hence, providing a revolutionary approach for diabetic wounds healing.