Peptide-Decorated Microneedles for the Detection of Microplastics.

The escalating utilization of plastics in daily life has resulted in pervasive environmental pollution and consequent health hazards. The challenge of detecting and capturing microplastics, which are imperceptible to the naked eye, is exacerbated by their diminutive size, hydrophobic surface properties, and capacity to absorb organic compounds. This study focuses on the application of peptides, constituted of specific amino acid sequences, and microneedles for the rapid and selective identification of microplastics. Peptides, due to their smaller size and greater environmental stability compared with antibodies, emerge as a potent solution to overcome the limitations inherent in existing detection methodologies. To immobilize peptides onto microneedles, this study employed microneedles embedded with gold nanorods, augmenting them with sulfhydryl (SH) groups at the peptides' termini. The sensor developed through this methodology exhibited efficient peptide binding to the microneedle tips, thereby facilitating the capture of microplastics. Raman spectroscopy was employed for the detection of microplastics, with the results demonstrating successful attachment to the microneedles. This novel approach not only facilitates localized analysis but also presents a viable strategy for the detection of microplastics across diverse environmental settings.

Liquid-Metal Core-Shell Particles Coated with Folate and Phospholipids for Targeted Drug Delivery and Photothermal Treatment of Cancer Cells.

Recently, several methods have been used for cancer treatment. Among them, chemotherapy is generally used, but general anticancer drugs may affect normal cells and tissues, causing various side effects. To reduce the side effects and increase the efficacy of anticancer drugs, a folate-based liquid-metal drug nanodelivery system was used to target the folate receptor, which is highly expressed in cancer cells. A phospholipid-based surface coating was formed on the surface of liquid-metal nanoparticles to increase their stability, and doxorubicin was loaded as a drug delivery system. Folate on the lipid shell surface increased the efficiency of targeting cancer cells. The photothermal properties of liquid metal were confirmed by near-infrared (NIR) laser irradiation. After treating cancerous and normal cells with liquid-metal particles and NIR irradiation, the particles were specifically bound to cancer cells for drug uptake, confirming photothermal therapy as a drug delivery system that is expected to induce cancer cell death through comprehensive effects such as vascular embolization in addition to targeting cancer cells.

Microtubule Acetylation-Specific Inhibitors Induce Cell Death and Mitotic Arrest via JNK/AP-1 Activation in Triple-Negative Breast Cancer Cells.

Microtubule acetylation has been proposed as a marker of highly heterogeneous and aggressive triple-negative breast cancer (TNBC). The novel microtubule acetylation inhibitors GM-90257 and GM-90631 (GM compounds) cause TNBC cancer cell death but the underlying mechanisms are currently unknown. In this study, we demonstrated that GM compounds function as anti-TNBC agents through activation of the JNK/AP-1 pathway. RNA-seq and biochemical analyses of GM compound-treated cells revealed that c-Jun N-terminal kinase (JNK) and members of its downstream signaling pathway are potential targets for GM compounds. Mechanistically, JNK activation by GM compounds induced an increase in c-Jun phosphorylation and c-Fos protein levels, thereby activating the activator protein-1 (AP-1) transcription factor. Notably, direct suppression of JNK with a pharmacological inhibitor alleviated Bcl2 reduction and cell death caused by GM compounds. TNBC cell death and mitotic arrest were induced by GM compounds through AP-1 activation in vitro. These results were reproduced in vivo, validating the significance of microtubule acetylation/JNK/AP-1 axis activation in the anti-cancer activity of GM compounds. Moreover, GM compounds significantly attenuated tumor growth, metastasis, and cancer-related death in mice, demonstrating strong potential as therapeutic agents for TNBC.

Tumor-derived miR-130b-3p induces cancer-associated fibroblast activation by targeting SPIN90 in luminal A breast cancer.

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) interact closely with cancer cells to promote tumor development. Downregulation of SPIN90 in CAFs has been reported to facilitate breast cancer progression, but the underlying mechanism has not been elucidated. Here, we demonstrate that miR-130b-3p directly downregulates SPIN90 in stromal fibroblasts, leading to their differentiation into CAFs. As the decrease of SPIN90 in CAFs was shown to be more prominent in estrogen receptor (ER)-positive breast tumors in this study, miR-130b-3p was selected by bioinformatics analysis of data from patients with ER-positive breast cancer. Ectopic expression of miR-130b-3p in fibroblasts accelerated their differentiation to CAFs that promote cancer cell motility; this was associated with SPIN90 downregulation. We also found that miR-130b-3p was generated in luminal A-type cancer cells and activated fibroblasts after being secreted via exosomes from cancer cells. Finally, miR-130b-3p increased in SPIN90-downregulated tumor stroma of luminal A breast cancer patients and MCF7 cell-xenograft model mice. Our data demonstrate that miR-130b-3p is a key modulator that downregulates SPIN90 in breast CAFs. The inverse correlation between miR-130b-3p and SPIN90 in tumor stroma suggests that the miR-130b-3p/SPIN90 axis is clinically significant for CAF activation during breast cancer progression.

Extra domain A-containing fibronectin expression in Spin90-deficient fibroblasts mediates cancer-stroma interaction and promotes breast cancer progression.

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment play major roles in supporting cancer progression. A previous report showed that SPIN90 downregulation is correlated with CAF activation and that SPIN90-deficient CAFs promote breast cancer progression. However, the mechanisms that mediate cancer-stroma interaction and how such interactions regulate cancer progression are not well understood. Here, we show that extra domain A (EDA)-containing fibronectin (FN), FN(+)EDA, produced by mouse embryonic fibroblasts (MEFs) derived from Spin90-knockout (KO) mice increases their own myofibroblast differentiation, which facilitates breast cancer progression. Increased FN(+)EDA in Spin90-KO MEFs promoted fibril formation in the extracellular matrix (ECM) and specifically interacted with integrin α4ß1 as the mediating receptor. Moreover, FN(+)EDA expression by Spin90-KO MEFs increased proliferation, migration, and invasion of breast cancer cells. Irigenin, a specific inhibitor of the interaction between integrin α4ß1 and FN(+)EDA, significantly blocked the effects of FN(+)EDA, such as fibril formation by Spin90-KO MEFs and proliferation, migration, and invasion of breast cancer cells. In orthotopic breast cancer mouse models, irigenin injection remarkably reduced tumor growth and lung metastases. It was supported by that FN(+)EDA in assembled fibrils was accumulated in cancer stroma of human breast cancer patients in which SPIN90 expression was downregulated. Our data suggest that SPIN90 downregulation increases FN(+)EDA and promotes ECM stiffening in breast cancer stroma through an assembly of long FN(+)EDA-rich fibrils; moreover, engagement of the Integrin α4ß1 receptor facilitates breast cancer progression. Inhibitory effects of irigenin on tumor growth and metastasis suggest the potential of this agent as an anticancer therapeutic.

SPIN90, an adaptor protein, alters the proximity between Rab5 and Gapex5 and facilitates Rab5 activation during EGF endocytosis.

During ligand-mediated receptor endocytosis, the small GTPase Rab5 functions in vesicle fusion and trafficking. Rab5 activation is known to require interactions with its guanine nucleotide-exchange factors (GEFs); however, the mechanism regulating Rab5 interactions with GEFs remains unclear. Here, we show that the SH3-adapter protein SPIN90 participates in the activation of Rab5 through the recruitment of both Rab5 and its GEF, Gapex5, to endosomal membranes during epidermal growth factor (EGF)-mediated endocytosis. SPIN90 strongly interacts with the inactive Rab5/GDI2 complex through its C-terminus. In response to EGF signaling, extracellular signal-regulated kinase (ERK)-mediated phosphorylation of SPIN90 at Thr-242 enables SPIN90 to bind Gapex5 through its N-terminal SH3 domain. Gapex5 is a determinant of Rab5 membrane targeting, while SPIN90 mediates the interaction between Gapex5 and Rab5 in a phosphorylation-dependent manner. Collectively, our findings suggest that SPIN90, as an adaptor protein, simultaneously binds inactive Rab5 and Gapex5, thereby altering their spatial proximity and facilitating Rab5 activation.