Intratumoral Bacterial-Targeted Cascade-Responsive Sonoafterglow Nanoprobes for Immune Reprogramming and Visualization in Glioblastoma.

Bacteria within glioblastoma (GBM) promote tumor progression and immunosuppression, while current treatments face challenges such as poor blood-brain barrier (BBB) penetration and immunosuppressive macrophages. To overcome these, we developed cascade-responsive sonoafterglow nanoprobes for bacteria-targeting, immune reprogramming, and imaging. These nanoprobes, incorporating a sonoafterglow pro-substrate, sonosensitizer, and maltodextrin, selectively targeted bacteria via the ATP-binding cassette sugar transporter pathway.

Electrically Driven Chimeric Extracellular Vesicles Crossing the Fundus Barrier for Retinoblastoma Treatment.

The internal limiting membrane (ILM), which separates the vitreous from the retina, hinders the delivery of extracellular vesicles (EVs) to the fundus via intravitreal injection for retinoblastoma treatment. In addition, EVs need to traverse biological barriers and selectively target retinoblastoma cells. To address these challenges, we designed an electroactive microneedle (e-MN) device to actively propel macrophage- and retinoblastoma-derived chimeric EVs across the ILM and precisely localize them to tumor cells.

Targeting α7 Nicotinic Acetylcholine Receptor for Modulating the Neuroinflammation of Dry Eye Disease Via Macrophages.

Purpose: Patients with dry eye disease (DED) often exhibit neurological abnormalities and may even suffer from neuropathic pain and pain-related anxiety or depression. The α-7 nicotinic acetylcholine receptor (α7nAChR) is a pivotal regulator in the anti-inflammatory pathway connecting the nervous and immune systems, Here, we investigate the potential of α7nAChR agonist as a novel treatment for DED.

Methods: We induced DED model by unilateral excision of extraorbital lachrymal gland in C57/BL6 mice.

Inflammation Targeting and Responsive Multifunctional Drug-Delivery Nanoplatforms for Combined Therapy of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent inflammation, joint swelling, pain, and progressive joint destruction. Methotrexate (MTX) is the standard first-line treatment for RA, but its clinical application is hindered by poor water solubility and non-specific delivery. In this work, a multifunctional drug-delivery nanoplatform that targets both macrophages and tumor necrosis factor α (TNFα) is developed to enhance the therapeutic efficacy of MTX in RA.

AI-assisted SERS imaging method for label-free and rapid discrimination of clinical lymphoma.

Background: Lymphoma is a malignant tumor of the immune system and its incidence is increasing year after year, causing a major threat to people's health. Conventional diagnosis of lymphoma basically depends on histological images consuming long-time and tedious manipulations (e.g.

A DNA Nanopatch-Bacteriophage System Targeting Streptococcus Gallolyticus for Inflammatory Bowel Disease Treatment and Colorectal Cancer Prevention.

Persistent inflammation in inflammatory bowel disease (IBD) increases Streptococcus gallolyticus (Sg) colonization, increasing the risk of colorectal cancer progression via the Sg-activated cyclooxygenase-2 (COX-2) pathway and β-catenin upregulation. This study presents Sg-specific bacteriophages modified with DNA nanopatches (DNPs@P) designed to treat IBD and prevent Sg-induced malignancy. The DNPs are composed of DNA origami nanosheets and phage capture strands.

Wearable electrodriven switch actively delivers macromolecular drugs to fundus in non-invasive and controllable manners.

Current treatments for fundus disorders, such as intravitreal injections, pose risks, including infection and retinal detachment, and are limited in their ability to deliver macromolecular drugs across the blood‒retinal barrier. Although non-invasive methods are safer, their delivery efficiency remains suboptimal (<5%). We have developed a wearable electrodriven switch (WES) that improves the non-invasive delivery of macromolecules to the fundus.

DNA Nanopatch-Specific Modification of Probiotics for Ultrasound-Triggered Inflammatory Bowel Disease Therapy.

Probiotics offer promising results for treating inflammatory bowel disease, yet precision therapy remains challenging, particularly in manipulating probiotics spatially and temporally and shielding them from oxidative stress. To address these limitations, herein we synthesized bacteria-specific DNA nanopatches to modify ultrasound-triggered engineered Nissle 1917. These probiotics produced the anti-inflammatory cytokine interleukin-10 when stimulated by ultrasound and were fortified with DNPs for oxidative stress resistance.

Enzyme-Responsive DNA Origami-Antibody Conjugates for Targeted and Combined Therapy of Choroidal Neovascularization.

Monotherapy, especially the use of antibodies targeting vascular endothelial growth factor (VEGF), has shown limitations in treating choroidal neovascularization (CNV) since reactive oxygen species (ROS) also exacerbate CNV formation. Herein, we developed a combination therapy based on a DNA origami platform targeting multiple components of ocular neovascularization. Our study demonstrated that ocular neovascularization was markedly suppressed by intravitreal injection of a rectangular DNA origami sheet modified with VEGF aptamers (Ap) conjugated to an anti-VEGF antibody (aV) via matrix metalloproteinase (MMP)-cleavable peptide linkers in a mouse model of CNV.

Defect-Rich Metastable MoS Promotes Macrophage Reprogramming in Breast Cancer: A Clinical Perspective.

Tumor-associated macrophages (TAMs) play a crucial function in solid tumor antigen clearance and immune suppression. Notably, 2D transitional metal dichalcogenides (i.e.

Photoactivated Gas-Generating Nanocontrast Agents for Long-Term Ultrasonic Imaging-Guided Combined Therapy of Tumors.

To date, long-term and continuous ultrasonic imaging for guiding the puncture biopsy remains a challenge. In order to address this issue, a multimodality imaging and therapeutic method was developed in the present study to facilitate long-term ultrasonic and fluorescence imaging-guided precision diagnosis and combined therapy of tumors. In this regard, certain types of photoactivated gas-generating nanocontrast agents (PGNAs), capable of exhibiting both ultrasonic and fluorescence imaging ability along with photothermal and sonodynamic function, were designed and fabricated.

Framework Nucleic Acids Combined with 3D Hybridization Chain Reaction Amplifiers for Monitoring Multiple Human Tear Cytokines.

Existing tear sensors are difficult to perform multiplexed assays due to the minute amounts of biomolecules in tears and the tiny volume of tears. Herein, the authors leverage DNA tetrahedral frameworks (DTFs) modified on the wireless portable electrodes to effectively capture 3D hybridization chain reaction (HCR) amplifiers for automatic and sensitive monitoring of multiple cytokines in human tears. The developed sensors allow the sensitive determination of various dry eye syndrome (DES)-associated cytokines in human tears with the limit of detection down to 0.

Inactive Trojan Bacteria as Safe Drug Delivery Vehicles Crossing the Blood-Brain Barrier.

K1 (EC-K1) can bypass the blood-brain barrier (BBB) and cause meningitis. Excitingly, we find the "dead EC-K1" can safely penetrate the BBB because they retain the intact structure and chemotaxis of the live EC-K1, while losing their pathogenicity. Based on this, we develop a safe "dead EC-K1"-based drug delivery system, in which EC-K1 engulf the maltodextrin (MD)-modified therapeutics through the bacteria-specific MD transporter pathway, followed by the inactivation via UV irradiation.

In vivo bioluminescence imaging of natural bacteria within deep tissues via ATP-binding cassette sugar transporter.

Most existing bioluminescence imaging methods can only visualize the location of engineered bacteria in vivo, generally precluding the imaging of natural bacteria. Herein, we leverage bacteria-specific ATP-binding cassette sugar transporters to internalize luciferase and luciferin by hitchhiking them on the unique carbon source of bacteria. Typically, the synthesized bioluminescent probes are made of glucose polymer (GP), luciferase, Cy5 and ICG-modified silicon nanoparticles and their substrates are made of GP and D-luciferin-modified silicon nanoparticles.

Camouflage Nanoparticles Enable Bioluminescence-Driven Optogenetic Therapy of Retinoblastoma.

Optogenetic therapy has emerged as a promising technique for the treatment of ocular diseases; however, most optogenetic tools rely on external blue light to activate the photoswitch, whose relatively strong phototoxicity may induce retinal damage. Herein, we present the demonstration of camouflage nanoparticle-based vectors for bioluminescence-driven optogenetic therapy of retinoblastoma. In biomimetic vectors, the photoreceptor CRY2 and its interacting partner CIB1 plasmid are camouflaged with folic acid ligands and luciferase NanoLuc-modified macrophage membranes.