Supramolecular gel with enhanced immunomodulatory effects presents a minimally invasive treatment strategy for eosinophilic chronic rhinosinusitis.

Background: Chronic rhinosinusitis (CRS) is an inflammatory disease characterized by persistent immune dysregulation, which presents considerable limitations in current medical therapy.

Objects: This study investigates a supramolecular gel (PSPD), which aims to minimize systemic adverse effects through local injection, provide long-lasting anti-inflammatory effects, and modulate the mucosal immune microenvironment.

Methods: The properties of PSPD were evaluated using rheological experiments.

Genetically engineered CD276-anchoring biomimetic nanovesicles target senescent escaped tumor cells to overcome chemoresistant and immunosuppressive breast cancer.

Chemotherapy-induced cellular senescence leads to an increased proportion of cancer stem cells (CSCs) in breast cancer (BC), contributing to recurrence and metastasis, while effective means to clear them are currently lacking. Herein, we aim to develop new approaches for selectively killing senescent-escape CSCs. High CD276 (95.

Controlled synthesized of ternary Cu-Co-Ni-S sulfides nanoporous network structure on carbon fiber paper: a superior catalytic electrode for highly-sensitive glucose sensing.

Background: Efficient monitoring of glucose concentration in the human body necessitates the utilization of electrochemically active sensing materials in nonenzymatic glucose sensors. However, prevailing limitations such as intricate fabrication processes, lower sensitivity, and instability impede their practical application. Herein, ternary Cu-Co-Ni-S sulfides nanoporous network structure was synthesized on carbon fiber paper (CP) by an ultrafast, facile, and controllable technique through on-step cyclic voltammetry, serving as a superior self-supporting catalytic electrode for the high-performance glucose sensor.

Sprayable, thermosensitive hydrogels for promoting wound healing based on hollow, porous and pH-sensitive ZnO microspheres.

A solvothermal method and the subsequent heat treatment process were developed to fabricate hollow ZnO particles with hierarchical pores on a large scale. The as-obtained hollow, porous ZnO microspheres with tunable sizes, high specific surface areas, pH sensitivity, antibacterial properties, and high adsorption capacities showed significant advantages for drug delivery. Sprayable hydrogels containing hollow, porous ZnO microspheres and curcumin nanoparticles (CNPs) were prepared to accelerate wound healing.

Thermosensitive gel-nano system against esophageal cancer via restoring p53 activity and boosting T-cell immunity.

In esophageal cancer (EC), clinical specimen testing has uncovered a significant increase in BTB and CNC homolog 1 (BACH1) expression and a shift towards an immunosuppressive environment, alongside a notable decrease in p53 protein expression. Therefore, therapeutic strategies focusing on BACH1 inhibition and p53 upregulation appear promising. Traditional oral treatments for EC lack precision and efficacy.

Mitochondria targeted drug delivery system overcoming drug resistance in intrahepatic cholangiocarcinoma by reprogramming lipid metabolism.

The challenge of drug resistance in intrahepatic cholangiocarcinoma (ICC) is intricately linked with lipid metabolism reprogramming. The hepatic lipase (HL) and the membrane receptor CD36 are overexpressed in BGJ398-resistant ICC cells, while they are essential for lipid uptake, further enhancing lipid utilization in ICC. Herein, a metal-organic framework-based drug delivery system (OB@D-pMOF/CaP-AC, DDS), has been developed.

Application of Dynamic Contrast-Enhanced Ultrasound in Evaluation the Activity of Crohn's Disease.

Background And Objective: The dynamic assessment of disease activity during the follow-up of patients with Crohn's disease (CD) remains a significant challenge. In this study, we aimed to identify the role of dynamic contrast-enhanced ultrasound (DCE-US) in the evaluation of activity of CD.

Methods: In the retrospective study, patients diagnosed with CD in our hospital were included.

Nanosystem Delivers Senescence Activators and Immunomodulators to Combat Liver Cancer.

CD47 blockade has emerged as a promising immunotherapy against liver cancer. However, the optimization of its antitumor effectiveness using efficient drug delivery systems or combinations of therapeutic agents remains largely incomplete. Here, patients with liver cancer co-expressing CD47 and CDC7 (cell division cycle 7, a negative senescence-related gene) are found to have the worst prognosis.

Long-acting anti-inflammatory injectable DEX-Gel with sustained release and self-healing properties regulates T1/T2 immune balance for minimally invasive treatment of allergic rhinitis.

Background: Allergic rhinitis (AR) is a prevalent immune-related allergic disease, and corticosteroid nasal sprays serve as the primary treatment for this patient population. However, their short duration of efficacy and frequent administration pose challenges, leading to drug wastage and potential adverse effects. To overcome these limitations, we devised a novel approach to formulate DEX-Gel by incorporating dexamethasone (DEX) into a blend of Pluronic F127, stearic acid (SA), and polyethylene glycol 400 (PEG400) to achieve sustained-release treatment for AR.

Dissolving microneedles-based programmed delivery system for enhanced chemo-immunotherapy of melanoma.

Immune checkpoint blockade, especially the programmed cell death ligand 1 (PD-L1) blockade, has revolutionized the treatment of melanoma. However, PD-1/PD-L1 monotherapy leads to unsatisfactory therapeutic outcomes. The immunotherapy of melanoma could be improved by adding doxorubicin (DOX), which triggers immunogenic cell death (ICD) effect to activate anti-tumor immunity.

Nano Ultrasound Contrast Agent for Synergistic Chemo-photothermal Therapy and Enhanced Immunotherapy Against Liver Cancer and Metastasis.

Advanced liver cancer is the most fatal malignant cancer, and the clinical outcomes of treatment are not very satisfactory due to the complexity and heterogeneity of the tumor. Combination therapy can efficiently enhance tumor treatment by stimulating multiple pathways and regulating the tumor immune microenvironment. Nanodrug delivery systems have become attractive candidates for combined strategies for liver cancer treatment.

Gut microbial metabolite butyrate improves anticancer therapy by regulating intracellular calcium homeostasis.

Background And Aims: Gut microbiota are recognized to be important for anticancer therapy, yet the underlying mechanism is not clear. Here, through the analysis of clinical samples, we identify the mechanism by which the gut microbial metabolite butyrate inhibits HCC and then explore new strategies for HCC treatment.

Approach And Results: In our study, we demonstrate that gut microbial metabolite butyrate improves anticancer therapy efficacy by regulating intracellular calcium homeostasis.

Deposition of hydrophilic TiCT on a superhydrophobic ZnO nanorod array for improved surface-enhanced raman scattering performance.

Background: Superhydrophobic substrate modifications are an effective way to improve SERS sensitivity by concentrating analyte molecules into a small surface area. However, it is difficult to manipulate low-volume liquid droplets on superhydrophobic substrates.

Results: To overcome this limitation, we deposited a hydrophilic TiCT film on a superhydrophobic ZnO nanorod array to create a SERS substrate with improved analyte affinity.

Inhibition of atherosclerosis progression by modular micelles.

Atherosclerosis is a chronic disease initiated by lipid-mediated vascular inflammation. From the perspective of conventional treatment, it is difficult to achieve good therapeutic effects via regulation of a single lipid or anti-inflammatory effects. Herein, we designed an amphiphilic low molecular weight heparin-unsaturated fatty acid conjugate (LMWH-uFA) that acted as both an antiatherosclerotic agent and a nanocarrier with self-delivery properties.

Overcoming AZD9291 Resistance and Metastasis of NSCLC via Ferroptosis and Multitarget Interference by Nanocatalytic Sensitizer Plus AHP-DRI-12.

The acquired resistance to Osimertinib (AZD9291) greatly limits the clinical benefit of patients with non-small cell lung cancer (NSCLC), whereas AZD9291-resistant NSCLCs are prone to metastasis. It's challenging to overcome AZD9291 resistance and suppress metastasis of NSCLC simultaneously. Here, a nanocatalytic sensitizer (VF/S/A@CaP) is proposed to deliver Vitamin c (Vc)-Fe(II), si-OTUB2, ASO-MALAT1, resulting in efficient inhibition of tumor growth and metastasis of NSCLC by synergizing with AHP-DRI-12, an anti-hematogenous metastasis inhibitor by blocking the amyloid precursor protein (APP)/death receptor 6 (DR6) interaction designed by our lab.

Systemic Delivery of mPEG-Masked Trispecific T-Cell Nanoengagers in Synergy with STING Agonists Overcomes Immunotherapy Resistance in TNBC and Generates a Vaccination Effect.

T-cell engagers (TCEs) represent a breakthrough in hematological malignancy treatment but are vulnerable to antigen escape and lack a vaccination effect. The "immunologically cold" solid tumor presents substantial challenges due to intratumor heterogeneity and an immunosuppressive tumor microenvironment (TME). Here, a methoxy poly(ethylene glycol) (mPEG)-masked CD44×PD-L1/CD3 trispecific T-cell nanoengager loaded with the STING agonist c-di-AMP (CDA) (PmTriTNE@CDA) for the treatment of triple-negative breast cancer (TNBC) is rationally designed.

Rapamycin-encapsulated costimulatory ICOS/CD40L-bispecific nanoparticles restrict pathogenic helper T-B-cell interactions while in situ suppressing mTOR for lupus treatment.

Excessive CD4 T helper (Th)-B-cell interactions and loss of Treg homeostasis are crucial to the pathogenesis of systemic lupus erythematosus (SLE). Targeting the SLE-specific upregulated costimulatory molecules ICOS or CD40L on Th can block Th-B reciprocal activation, but single costimulatory molecular blockade exhibited unsatisfactory therapeutic efficacy due to pathway redundancy. As ICOS and CD40L nonredundantly and cooperatively promote Th-B-cell reciprocal activation, simultaneously blocking ICOS and CD40L may achieve a synergistic effect.

Programmed prodrug breaking the feedback regulation of P-selectin in plaque inflammation for atherosclerotic therapy.

Inflammation is the main driver of the aggravation of arteriosclerosis, and the complex inflammatory response in plaque is usually the result of the interaction of various cells and cytokines. Therefore, it is difficult to comprehensively regulate the inflammatory process of arteriosclerosis by intervening a single target, resulting in the poor effect of existing treatment method. Based on our clinical findings that P-selectin stably and highly expressed in patients' plaque endothelial cells, the programmed prodrug, low molecular weight heparin-indomethacin nanoparticles (LI NPs), were established as anti-inflammatory agent to multiphase inhibit arteriosclerosis by cascade interference of P-selectin.

Engineered PD-1/TIGIT dual-activating cell-membrane nanoparticles with dexamethasone act synergistically to shape the effector T cell/Treg balance and alleviate systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a potentially life-threatening autoimmune disease that is characterized by alterations in the balance between effector and regulatory CD4 T cells. We observed the upregulation of the immune checkpoints (ICs) PD-1 and TIGIT in pathogenic CD4 T cells during disease progression, and downregulation of their ligands PD-L1 and CD155. Inspired by biomimetic nanotechnology, we fabricated dexamethasone (DXM)-loaded IFN-γ-treated MHC class I deficient cancer membrane-coated nanoparticles (IM-MNPs/DXM) to safely harness the immunosuppressive power of tumor cells for the treatment of SLE.

Nano-ultrasonic Contrast Agent for Chemoimmunotherapy of Breast Cancer by Immune Metabolism Reprogramming and Tumor Autophagy.

The functional status of innate immune cells is a considerable determinant of effective antitumor immune response. However, the triple-negative breast cancer tumor microenvironment with high lactic acid metabolism and high antioxidant levels limits immune cell survival, differentiation, and function. Here, we determine that the tumor microenvironment-responsive nano-ultrasonic contrast agent Pt(IV)/CQ/PFH NPs-PPA-1 boosts the ratio of mature dendritic cells (mDCs) and proinflammatory macrophages by reprogramming the metabolism of immature DCs (iDCs) and tumor-associated macrophages (TAMs).

Exosome-liposome hybrid nanoparticle codelivery of TP and miR497 conspicuously overcomes chemoresistant ovarian cancer.

Background: Although cisplatin-based chemotherapy has been used as the first-line treatment for ovarian cancer (OC), tumor cells develop resistance to cisplatin during treatment, causing poor prognosis in OC patients. Studies have demonstrated that overactivation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is involved in tumor chemoresistance and that overexpression of microRNA-497 (miR497) may overcome OC chemotherapy resistance by inhibiting the mTOR pathway. However, the low transcriptional efficiency and unstable chemical properties of miR497 limit its clinical application.

ROS-responsive dexamethasone micelles normalize the tumor microenvironment enhancing hypericin in cancer photodynamic therapy.

The efficacy of photodynamic therapy (PDT) for cancer is limited owing to the abnormality of the tumor microenvironment (TME), such as the dysfunctional tumor vascular system leading to restricted drug distribution in tumor lesions, and hypoxia resulting in hampering the application of the photosensitizer because of the shortage of oxygen. Therefore, normalizing the TME is a novel strategy for enhancing the therapeutic efficacy of PDT. Herein, we designed and fabricated reactive oxygen species (ROS)-responsive micelles with a self-circulating release manner to co-deliver a glucocorticoid steroid dexamethasone (DXM) and a photosensitizer hypericin (HYP) (denoted as HDTM).