Hyaluronic acid act as drug self-assembly chaperone and co-assembled with celalstrol for ameliorating non-alcoholic steatohepatitis.

Nanoformulations of therapeutic drugs with diverse chemical structures are often complex to produce and lack a universal synthesis approach. Herein, we demonstrate that hyaluronic acid (HA) can function as an assembly chaperone, facilitating the formulation of various chemical compounds into nanoparticles without necessitating chemical modification. As a proof of concept, celastrol-HA co-assembled nanoparticles (CHNPs) were synthesized and utilized in the multifactorial treatment of non-alcoholic steatohepatitis (NASH).

Guanidine-Derived Polymeric Nanoinhibitors Target the Lysosomal V-ATPase and Activate AMPK Pathway to Ameliorate Liver Lipid Accumulation.

Current research efforts in polymer and nanotechnology applications are primarily focused on cargo delivery to enhance the therapeutic index, with limited attention being paid to self-molecularly targeted nanoparticles, which may also exhibit significant therapeutic potential. Long-term and anomalous lipid accumulation in the liver is a highly relevant factor contributing to liver diseases. However, the development of the reliable medications and their pharmacological mechanisms remain insufficient.

Ursodeoxycholic acid loaded dual-modified graphene oxide nanocomposite alleviates cholestatic liver injury through inhibiting hepatocyte apoptosis.

Ursodeoxycholic acid (UDCA) is the preferred treatment for various types of cholestasis, however, its effectiveness is limited because of its insolubility in water. We used polyethylene glycol (PEG) and cationic polymer polyethylenimine (PEI) to double-modify graphite oxide (PPG) as a drug delivery system. UDCA was successfully loaded onto PPG through intermolecular interactions to form UDCA-PPG nanoparticles.

Ox-LDL-induced CD80 macrophages expand pro-atherosclerotic NKT cells via CD1d in atherosclerotic mice and hyperlipidemic patients.

Atherosclerosis is an inflammatory disease of blood vessels involving the immune system. Natural killer T (NKT) cells, as crucial components of the innate and acquired immune systems, play critical roles in the development of atherosclerosis. However, the mechanism and clinical relevance of NKT cells in early atherosclerosis are largely unclear.

Red/NIR-I-Fluorescence Carbon Dots Based on Rhein with Active Oxygen Scavenging and Colitis Targeting for UC Therapeutics.

Ulcerative colitis (UC) is a chronic inflammatory disease with uncontrolled inflammation and demage to the intestinal barrier. Rhein, a bioactive compound in traditional Chinese medicine, has anti-inflammatory and intestinal repair effect. However, their clinical application is limited by their hydrophobicity and poor bioavailability.

Dual-monomer solvatochromic probe system (DSPS) for effectively differentiating lipid raft cholesterol and active membrane cholesterol in the inner-leaflet plasma membrane.

Monitoring active membrane cholesterol and lipid raft cholesterol in the inner leaflet of the plasma membrane is significant for understanding the membrane function and cellular physiopathological processes. Limited by existing methods, it is difficult to differentiate active membrane cholesterol and lipid raft cholesterol. A novel dual-monomer solvatochromic probe system (DSPS) that targets two types of cholesterol was developed.

Proteolysis Targeting Chimeras (PROTACs) based on celastrol induce multiple protein degradation for triple-negative breast cancer treatment.

The pursuit of single drugs targeting multiple targets has become a prominent trend in modern cancer therapeutics. Natural products, known for their multi-targeting capabilities, accessibility, and cost-effectiveness, hold great potential for the development of multi-target drugs. However, their therapeutic efficacy is often hindered by complex structural modifications and limited anti-tumor activity.

A hydrogel system for drug loading toward the synergistic application of reductive/heat-sensitive drugs.

The preparation of hydrogels as drug carriers via radical-mediated polymerization has significant prospects, but the strong oxidizing ability of radicals and the high temperatures generated by the vigorous reactions limits the loading for reducing/heat-sensitive drugs. Herein, an applicable hydrogel synthesized by radical-mediated polymerization is reported for the loading and synergistic application of specific drugs. First, the desired sol is obtained by polymerizing functional monomers using a radical initiator, and then tannic-acid-assisted specific drug mediates sol-branched phenylboric acid group to form the required functional hydrogel (New-gel).

Functional molecule-mediated assembled copper nanozymes for diabetic wound healing.

Background: The complex hyperglycemic, hypoxic, and reactive oxygen species microenvironment of diabetic wound leads to vascular defects and bacterial growth and current treatment options are relatively limited by their poor efficacy.

Results: Herein, a functional molecule-mediated copper ions co-assembled strategy was constructed for collaborative treatment of diabetic wounds. Firstly, a functional small molecule 2,5-dimercaptoterephthalic acid (DCA) which has symmetrical carboxyl and sulfhydryl structure, was selected for the first time to assisted co-assembly of copper ions to produce multifunctional nanozymes (Cu-DCA NZs).

A dual-lock-controlled mitochondria-targeted ratiometric fluorescence probe for simultaneous detection of atherosclerosis-related HClO and viscosity.

Precise detection of inflammatory microenvironment-related viscosity and hypochlorous acid (HClO) contributes to illuminating the pathogenesis and further diagnosing of atherosclerosis (AS). Herein, a dual-lock-controlled mitochondria-targeted fluorescence probe (NS) for simultaneous imaging of HClO and viscosity in AS-related foam cells is presented. NS performs linear increase in green-fluorescence along with increased viscosity (excited at 425 nm), permitting "off-on" fluorescence imaging of viscosity.

CES1-Triggered Liver-Specific Cargo Release of CRISPR/Cas9 Elements by Cationic Triadic Copolymeric Nanoparticles Targeting Gene Editing of PCSK9 for Hyperlipidemia Amelioration.

The broad application of clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 genome editing tools is hindered by challenges in the efficient delivery of its two components into specific cells and intracytoplasmic release. Herein, a novel copolymer for delivery of Cas9-mRNA/ single-guide RNA (Cas9-mRNA/sgRNA) in vitro and vivo, using carboxylesterase-responsive cationic triadic copolymeric nanoparticles targeted proprotein convertase subtilisin/kexin type 9 (PCSK9) for hyperlipidemia amelioration is reported. A dimethyl biguanide derivative is designed and synthesized to form cationic block, and copolymerization onto prepolymer with propyl methacrylate, to fabricate a triadic copolymer mPEG-b-P(Met/n-PMA).

Copper-rich multifunctional Prussian blue nanozymes for infected wound healing.

The healing process of infected wounds was limited by bacterial infection, excessive reactive oxygen species (ROS) accumulation, and tissue hypoxia. In order to alleviate the above situations, herein, a copper-rich multifunctional ultra-small Prussian blue nanozymes (HPP@Cu NZs) was constructed for infected wound synergistic treatment. Firstly, hyaluronic acid was modified by branched polyethyleneimine which could form a complex with copper ions, to construct copper-rich Prussian blue nanozymes.

Quercetin Suppresses Human Glioblastoma Migration and Invasion via GSK3β/β-catenin/ZEB1 Signaling Pathway.

High invasiveness is a biological and clinical characteristic of glioblastoma and predicts poor prognosis of patients. Quercetin, a natural flavonoid compound, exhibits anticancer activity. However, we have a limited understanding of the possible underlying mechanism of quercetin in glioblastoma.

Small molecule-assisted assembly of multifunctional ceria nanozymes for synergistic treatment of atherosclerosis.

Considering that intravascular reactive oxygen species (ROS) and inflammation are two characteristic features of the atherosclerotic microenvironment, developing an appropriate strategy to treat atherosclerosis by synergistically regulating ROS and inflammation has attracted widespread attention. Herein, a special molecule, zoledronic acid, containing imidazole and bisphosphonate groups, was selected for the first time to assist the assembly of cerium ions and produce functionalized ceria-zoledronic acid nanocomposites (CZ NCs). It not only serves as a new carrier for different kinds of drugs (e.

Dual-Emission ZAISe/ZnS quantum dots for Multi-level Bio-Imaging: Foam cells and atherosclerotic plaque imaging.

In vitro or in vivo fluorescence imaging based on quantum dots (QDs) has shown promise for the noninvasive diagnosis of atherosclerosis. However, simultaneous in vitro and in vivo imaging remains challenging due to the limitation of the current synthesis method of dual-emission QDs (dual-emitting hybrid QDs, and broad-spectrum emitting QDs). Herein, we fabricate a dual-emission (visible region and near-infrared region emission) QDs (ZAISe/ZnS) via the "bottom to up" method of a quaternary inorganic compound for the foam cells and atherosclerosis plaque imaging simultaneously without the intricate size modulation and the strict optical filter requirements.

Biomimetic macrophage membrane-coated gold-quantum dots with tumor microenvironment stimuli-responsive capability for tumor theranostic.

Tumor microenvironment (TME) is intently related to tumor growth, progression and invasion, leading to drug resistance and insufficient therapeutic efficacy. However, remodeling TME and utilizing TME for exploring intelligent nanomaterials that can realize tumor theranostic is still challenging. Nowadays, the theranostic based on chemotherapy exposes some deficiencies, such as low targeting, weak permeability and premature clearance.

A targeting mesoporous dopamine nanodrug platform with NIR responsiveness for atherosclerosis improvement.

Atherosclerosis (AS), the formation of plaque lesions in the walls of arteries, causes many mortalities and morbidities worldwide. Currently, achieving site-specific delivery and controlled release at plaques is difficult. Herein, we implemented the strategy of constructing a bionic multifunctional nanoplatform (BM-NP) for targeting and improving plaques.

Blood-brain barrier penetrating carbon dots with intrinsic anti-inflammatory and drug-loading properties.

The blood-brain barrier (BBB) is the major obstacle limiting the reach of therapeutic drugs into the brain. Herein, an aspirin-based anti-inflammatory replenisher (aspCD) was fabricated by carbonizing aspirin to deliver drugs into the brain visually. The as-prepared aspCD combined the BBB-penetrating and anti-inflammatory effects of aspirin with the fluorescent and drug-loading properties of carbon dots (CDs), thereby delivering therapeutic drugs into the brain and acting as imaging agent as well as anti-inflammatory replenisher.

Intracellular K-Responsive Block Copolymer Micelles for Targeted Drug Delivery of Curcumin.

Curcumin (CUR) is a natural bioactive compound that has attracted attention as a "golden molecule" due to its therapeutic properties against several types of tumors. Nonetheless, the antitumor application of CUR is hampered due to its extremely low aqueous solubility and chemical instability. Herein, a novel type of CUR-loaded polymeric micelles with intracellular K-responsive controlled-release properties is designed and developed.

Targeted intelligent mesoporous polydopamine nanosystems for multimodal synergistic tumor treatment.

Developing intelligent responsive platforms to carry out high-performance therapy is of great interest for the treatment of tumors and their metastases. However, effective drug loading, activity maintenance, off-target leakage, and response to collaborative therapy remain great challenges. Herein, a targeted intelligent responsive mesoporous polydopamine (MPDA) nanosystem was reported for use in gene-mediated photochemotherapy for synergistic tumor treatment.

Self-assembly drug-albumin nanocomposites for nonalcoholic fatty liver disease treatment.

Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic liver disease closely related to obesity, which has become a global health problem. However, current pharmacological therapies for NAFLD are limited by potential side effects, low effectiveness and poor aqueous solubility. Herein, we designed functionalized drug-albumin nanocomposites (BAM15@BSA NPs), which were prepared by self-assembly of the anti-obesity small-molecule drug (BAM15) and bovine serum albumin (BSA), for treatment of NAFLD.

Glucose/ROS cascade-responsive ceria nanozymes for diabetic wound healing.

Diabetic wounds have an extremely complex microenvironment of hyperglycemia, hypoxia and high reactive oxygen species (ROS). Therefore, the regulation and management of this microenvironment may provide a new and improved treatment method for chronic diabetic wound healing. Herein, a glucose/ROS cascade-responsive nanozyme (CHA@GOx) was developed for diabetic wound treatment based on Ce-driven coassembly by a special dual ligand (alendronic acid and 2-methylimidazole) and glucose oxidase (GOx).

ZIF-based carbon dots with lysosome-Golgi transport property as visualization platform for deep tumour therapy hierarchical size/charge dual-transform and transcytosis.

The poor penetration of nanomaterials in solid tumours and difficulty in monitoring their penetration depth are major obstacles in their application for the treatment of solid tumours. Herein, pH-responsive carbon dots (ZCD) based on a zeolitic imidazolate framework (ZIF-8) were fabricated to achieve the deep delivery of the chemotherapeutic doxorubicin (DOX) a hierarchical size/charge dual-transformation and transcytosis. The as-prepared ZCD accumulated in the solid tumour and the acidic tumour microenvironment further triggered its decomposition.

Antigen-Presenting Cell-Like Neutrophils Foster T Cell Response in Hyperlipidemic Patients and Atherosclerotic Mice.

Neutrophils constitute abundant cellular components in atherosclerotic plaques. Most of the current studies are focused on the roles of granular proteins released by neutrophils in atherosclerosis. Here, we revealed a unique subset of neutrophils which exhibit the characteristics of antigen-presenting cell (APC) (which were called APC-like neutrophils afterwards) in atherosclerosis.