Therapeutic co-assemblies for synergistic NSCLC treatment through dual topoisomerase I and tubulin inhibitors.

Camptothecin (CPT) and podophyllotoxin (PPT) function as topoisomerase (TOP) I and tubulin inhibitors, respectively, with potent anticancer effects in a variety of cancers. Despite its promise, the clinical applicability of the combination of CPT and PPT faces challenges, including potential side effect and limited therapeutic efficacy. In this study, we designed co-assembly nanomedicines with the different weight (w/w) ratios of amphiphilic Evans blue conjugated CPT prodrug (EB-ss-CPT) and PPT molecules, denoted as ECT Nano.

Hydrogel-Mediated Jamming of Exosome Communications That Counter Tumor Adaption in the Tumor Immune Microenvironment.

Hypoxia, a common occurrence within solid tumors, can stimulate the dissemination of deceptive tumor exosomes, which function as communicative bridges and orchestrate the recruitment of various supportive cell types for enhanced tumor adaptability in a tumor immune microenvironment. Current nanotechnology provides us intelligent strategies to combat the hypoxic tumor microenvironment. However, once exposed to external stimuli, such as chemotherapy, tumor cells simultaneously release malignant signals to develop tumor migration and immunosuppression, posing challenges to clinical practice.

Ultrasmall Nanodots with Dual Anti-Ferropototic Effect for Acute Kidney Injury Therapy.

Ferroptosis is known to mediate the pathogenesis of chemotherapeutic drug-induced acute kidney injury (AKI); however, leveraging the benefits of ferroptosis-based treatments for nephroprotection remains challenging. Here, ultrasmall nanodots, denoted as FerroD, comprising the amphiphilic conjugate (tetraphenylethylene--serine-deferoxamine, TPE-lys-Ser-DFO (TSD)) and entrapped ferrostatin-1 are designed. After being internalized through kidney injury molecule-1-mediated endocytosis, FerroD can simultaneously remove the overloaded iron ions and eliminate the overproduction of lipid peroxides by the coordination-disassembly mechanisms, which collectively confer prominent inhibition efficiency of ferroptosis.

Injectable Hydrogel Mucosal Vaccine Elicits Protective Immunity against Respiratory Viruses.

Intranasal vaccines, eliciting mucosal immune responses, can prevent early invasion, replication, and transmission of pathogens in the respiratory tract. However, the effective delivery of antigens through the nasal barrier and boosting of a robust systematic and mucosal immune remain challenges in intranasal vaccine development. Here, we describe an intranasally administered self-healing hydrogel vaccine with a reversible strain-dependent sol-gel transition by precisely modulating the self-assembly processes between the natural drug rhein and aluminum ions.

Coassembly Nanomedicine Mediated by Intermolecular Interactions Between Methotrexate and Baricitinib for Improved Rheumatoid Arthritis Treatment.

The combination of anti-rheumatoid arthritis (RA) drugs methotrexate (MTX) and baricitinib (BTN) has been reported to improve RA treatment efficacy. However, study on the strategy of combination is elusive when considering the benefit of the synergy between MTX and BTN. In this study, we found that the N-heterocyclic rings in the MTX and BTN offer hydrogen bonds and π-π stacking interactions, driving the formation of exquisite vesicular morphology of nanovesicles, denoted as MB NVs.

Magnetic Resonance Imaging Nanoprobe Quantifies Nitric Oxide for Evaluating M1/M2 Macrophage Polarization and Prognosis of Cancer Treatments.

Macrophages play a crucial role in immune activation and provide great value in the prognosis of cancer treatments. Current strategies for prognostic evaluation of macrophages mainly target the specific biomarkers to reveal the number and distribution of macrophages in the tumors, whereas the phenotypic change of M1 and M2 macrophages is less understood. Here, we designed an ultrasmall superparamagnetic iron oxide nanoparticle-based molecular imaging nanoprobe to quantify the repolarization of M2 to M1 macrophages by magnetic resonance imaging (MRI) using the redox-active nitric oxide (NO) as a vivid chemical target.

Ferroptosis Detection: From Approaches to Applications.

Understanding the intricate molecular machinery that governs ferroptosis and leveraging this accumulating knowledge could facilitate disease prevention, diagnosis, treatment, and prognosis. Emerging approaches for the in situ detection of the major regulators and biological events across cellular, tissue, and in living subjects provide a multiscale perspective for studying ferroptosis. Furthermore, advanced applications that integrate ferroptosis detection and the latest technologies hold tremendous promise in ferroptosis research.

Arsenic retention in erythrocytes and excessive erythrophagocytosis is related to low selenium status by impaired redox homeostasis.

Arsenic (As) contamination in drinking water is a global public health problem. Epidemiological studies have shown that selenium (Se) deficiency is associated with an increasing risk of arsenism. However, the association between Se status and As retention in erythrocytes and mechanisms underlying this association have not been fully investigated.

The RIT2 and STX1B polymorphisms are associated with Parkinson's disease.

Introduction: GWAS meta-analysis identified RIT2 rs12456492 and STX1B rs4889603 as PD susceptible loci. While proteins encoded by the genes, in particular RIT2, may involve in PD pathogenesis, the association of these two variants with PD remains to be further clarified.

Methods: We enrolled a Chinese cohort comprising 537 PD patients and 517 controls, determined the genotypes of rs12456492 and rs4889603, and analyzed these variants in relation to PD.