artesunate (artesunate, Amivas)

Artesunate targets STAT3 to alleviate Hodgkin's lymphoma via JAK-STAT/PD-L1 axis.

Chen Di D, Zhang Geng G, San Jinghui J, Liu Baoru B et al.

Relapsed or refractory Hodgkin lymphoma (HL) is resistant to existing chemotherapy and PD-1 inhibitors, creating an urgent need for safe and effective drugs with novel mechanisms of action. Artesunate (ART), a classic antimalarial agent, has recently demonstrated broad-spectrum antitumor activity. However, its direct targets and core molecular mechanisms in HL remain unclear. In this study, we combined HuProt™ 20 K human proteome microarray, network pharmacology, molecular docking, and in vitro functional assays to identify the key targets and signaling pathways of ART against HL. Critical functional residues were validated through site-directed mutagenesis. Proteome microarray and protein-protein interaction network analysis identified STAT3 as the core target of ART in HL. Molecular docking revealed a binding energy of -7.2 kcal/mol between ART and STAT3, with Glu638 identified as a critical interacting residue. Functional experiments confirmed that ART significantly inhibited STAT3 phosphorylation, reduced the levels of soluble PD-L1, BCL-XL, and IL-6 in the supernatant, and suppressed HL cell proliferation and migration. Notably, both the STAT3E638A mutation and STAT3-siRNA completely abolished the antitumor effects of ART. Collectively, ART blocks the JAK-STAT/PD-L1 signaling axis by targeting Glu638 of STAT3, achieving dual effects of inhibiting tumor survival and reversing immune evasion. This work identifies STAT3 as a direct binding target of ART in HL and establishes Glu638 as a critical functional site, providing a robust theoretical and experimental foundation for repurposing ART in the treatment of relapsed or refractory HL.

Precursor-Encoded Metal-Free Carbon Dots Reshape the Bone-Regenerative Microenvironment: Materials Chemistry, Multiscale Mechanisms, and a Translational Roadmap.

Wang Yang Y, Liang Nai N, Cai Baisheng B, Jiang Su S

Bone-defect healing is a spatiotemporally coordinated continuum involving inflammatory initiation and resolution, redox re-equilibration, immune-cell state transitions, angiogenesis, osteogenic commitment of mesenchymal stromal/progenitor cells, and osteoblast-osteoclast coupling. Although metal-containing nanomaterials can enhance regeneration through ion release, catalysis, or photothermal effects, their performance is often constrained by local dose, oxidation state, release kinetics, and long-term accumulation. Metal-free carbon dots (CDs) combine nanoscale interfacial activity, programmable surface chemistry, electron-transfer capacity, intrinsic fluorescence, and scaffold compatibility and are consequently evolving from imaging probes into bioactive regulators of the bone-repair microenvironment. Following the sequence of precursor chemistry-carbonization reconstruction-surface state-protein corona/organelle response-tissue regeneration, this review compares CDs derived from citric acid, ascorbic acid, amino acids, curcumin, artesunate, yam, clove, ginger, and other natural or medicinal-food precursors. We critically examine context-dependent redox regulation, macrophage-state remodeling, osteogenic and epigenetic control, suppression of pathological osteoclastogenesis, infection control, and angiogenesis-osteogenesis coupling. Current evidence is limited by ambiguous structural identity, confounded activity attribution, correlation-dominant mechanisms, overextension from simplified models, and insufficient long-term safety assessment. Translation will require fractionation-based identity definition, multi-batch potency assays, target-protein capture, organelle tracking, genetic rescue, spatial omics, and quantitative integration of chemistry, local exposure, degradation/clearance, and regenerative efficacy. Particular attention is given to how CD surface states interact with collagen, fibrin, and glycosaminoglycan matrices to govern protein adsorption, local retention, matrix organization, and growth-factor presentation. A two-tier evidence roadmap is proposed, prioritizing fraction-resolved activity attribution, compartment-specific redox assays, post-formulation identity testing, and context-matched progression from screening defects to load-bearing and comorbidity models.

Availability of IV Artesunate for Severe Malaria.

Smith Bryan L BL, Novitt-Moreno Anne D AD

Dual-Targeting Nanomicelles Co-Loading Sorafenib and Artesunate Combats Hepatocellular Carcinoma via the Synergistically Enhanced Ferroptosis Strategy.

Lu Wangjing W, Yang Juan J, Mi Jinxia J, Luo Fazhen F et al.

Hepatocellular carcinoma (HCC) remains a formidable malignancy with limited response to conventional monotherapies, largely due to its complicated pathogenesis and useful cellular defense systems. In this study, we constructed a dual-targeting polymeric micelle (S&A@TPD/HG PMs), co-delivering sorafenib (SOR), and artesunate (ART) to achieve synergistic ferroptosis-based therapy against HCC. The micelle features a hyaluronic acid (HA) shell functionalized with glycyrrhetinic acid (GA) for active dual targeting to CD44 and GA receptors overexpressed on HCC cells; while its triphenylphosphonium (TPP)-decorated inner core facilitates mitochondrial anchoring and co-conveys the drugs, enabling stepwise subcellular targeting. Compared with free drugs or single-drug-loaded micelles, S&A@TPD/HG PMs effectively induced mitochondrial damage by depleting glutathione (GSH), and downregulating GSH peroxidase 4 (GPX4) expression to disrupt the mitochondrial antioxidant defense system, elevating intracellular Fe2+ to increase reactive oxygen species (ROS) and lipid peroxidation (LPO) production, thereby compromising mitochondrial redox homeostasis and potentiating ferroptosis jointly. This ferroptosis-inducing activity yielded potent in vivo antitumor efficacy in Huh-7 tumor-bearing nude mice, with a tumor inhibition rate of 74.23% and minimal systemic toxicity. Collectively, the organelle-specific targeting combined with co-delivery of synergistic drug pairs represents a promising strategy for combating malignancies and provides a blueprint for the rational design of multifunctional nanosystems.