Myelosuppression is a common and severe side effect of cancer chemotherapy, with current treatments hindered by limitations such as depletion of hematopoietic reserves, poor patient compliance, delayed therapeutic onset, and high cost. To overcome these challenges, we developed Epimedium-derived nanovesicles (ENVs) from the traditional Chinese medicinal herb Epimedium, addressing the solubility and bioavailability issues associated with conventional extracts. ENVs encapsulate bioactive constituents, including icariin and hematopoiesis-promoting ceramides. In a cyclophosphamide (CTX)-induced myelosuppression mouse model, prophylactic and therapeutic oral administration of ENVs effectively alleviated hematopoietic suppression, significantly outperforming the Epimedium-based herbal extract “Joungal” (Shengbai Formula) despite equivalent icariin content. Notably, ENVs promoted hematopoietic stem cell (HSC) proliferation—an outcome rarely achieved with existing therapies. Mechanistically, ENVs modulated the gut microbiota, enriching lactobacillus species and enhancing lactate production. This microbiota-driven lactate signaling stimulated LepR⁺ mesenchymal stem cells (MSCs) in the bone marrow niche to secrete stromal cell-derived factor-1 (SDF-1) and stem cell factor (SCF), thereby supporting HSC expansion and restoring hematopoietic function. In vivo safety evaluations confirmed the excellent biocompatibility of ENVs. Our findings uncover a gut–lactate–bone marrow axis through which ENVs enhance hematopoiesis and promote HSC regeneration. This work introduces a cost-effective, scalable, and orally administrable biomaterial platform with strong translational potential for the prevention and treatment of chemotherapy-induced myelosuppression.

Acute kidney injury (AKI) has high incidence and mortality rates, with its vicious cycle involving inflammation, oxidative stress, and apoptosis often leading to rapid decline in renal function. Current treatments face multiple challenges: lack of targeted drugs, limited efficacy of conventional therapies with significant systemic side effects, difficulty in drug delivery to the kidney's unique structure, susceptibility to re-injury, rapid disease progression, a narrow intervention window, and high risk of irreversible damage. To address these issues, we developed the near-infrared II (NIR-II)-excited photothermal nanocomposite Cu_2–XSe@AHI. Constructed via coordination self-assembly, this material offers advantages of structural controllability, spatiotemporal precision, and non-invasive treatment. Upon NIR-II laser activation, it achieves deep tissue penetration and low-toxicity photothermal conversion, generating mild thermal stimulation in the kidney to specifically induce heat shock protein 70 (HSP70) expression. HSP70 stabilizes the inhibitor of κB alpha–IκB kinase beta (IκBα–IKKβ) complex, inhibiting the nuclear factor kappa-B (NF-κB) pathway to synergistically exert anti-inflammatory, antioxidant, and anti-apoptotic effects. Furthermore, HSP70 upregulation enhances cellular resilience and promotes tissue repair, enabling a dual mechanism from injury blockade to active restoration. This strategy overcomes limitations of existing therapies, offering a novel pathway with high translational potential for AKI treatment.

Metabolic-associated fatty liver disease (MAFLD), a global health burden with limited therapeutic options beyond lifestyle changes, urgently needs novel strategies. We engineered exosome-like nanovesicles (HNVs) from dried honeysuckle (Lonicera japonica), exhibiting significantly more uniform size distribution than conventional herbal extracts and characteristic nanovesicle morphology. Orally delivered HNVs, enriched with bioactive metabolites, dramatically inhibited increased fat vacuoles, lipid droplet deposition, and collagen fibrosis in the livers of mice with MAFLD induced by high-fat diet (HFD). Mechanistically, HNVs orchestrate a dual gut-liver intervention: (1) restoring gut barrier integrity, slashing serum LPS by 1.58-fold and quelling hepatic inflammation; (2) remodeling gut microbiota to suppress bile salt hydrolase (BSH), elevating taurochenodeoxycholic acid (TCDCA) 2.07-fold. This microbial shift reprograms enterohepatic signaling by inhibiting the FXR-FGF15-FGFR4 axis, thereby boosting hepatic cholesterol catabolism via bile acid synthases. Critically, efficacy is strictly microbiota-dependent: abolished by antibiotics and fully transferable via fecal microbiota transplantation (FMT) from HNV-treated donors. Presenting the first natural nanovesicle platform that concurrently targets gut barrier repair and metabolic reprogramming, HNVs establish a pioneering, multi-targeted therapeutic paradigm for MAFLD, directly linking gut microbial ecology to hepatic pathophysiology with high translational potential.

Cisplatin (CDDP)-based chemotherapy is substantially limited in the clinic due to its high postoperative recurrence rate. Synergy therapy has been proven as a potent approach to minimize recurrence and achieve enhanced treatment effects. Herein, chemotherapy drug CDDP is assembled with the photothermal-Fenton agent of bovine serum albumin (BSA) stabilized gallic acid-functionalized iron nanoparticles (GA-Fe NPs) to achieve chemo/chemodynamic synergistic cascade oncotherapy. The Pt-GA-Fe NPs can be utilized to generate H₂O₂ via the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) in the tumor microenvironment (TME), which would then greatly boost H₂O₂-depending chemodynamic therapy (CDT). The generated cytotoxic reactive oxygen species (hydroxyl radicals, ·OH) and the depletion of glutathione (GSH) would further promote CDDP-induced DNA damage. Moreover, benefiting from the absorption in the near-infrared (NIR) region, Pt-GA-Fe NPs exhibit excellent photothermal conversion efficiency (η = 45.5%) and allow photoacoustic imaging (PAI) guided photothermal therapy (PTT). In vitro and in vivo experiments show that synergy therapy can effectively kill cancer cells and successfully cure cancer without systemic toxicity. The work highlights a new type of therapeutic agent based on CDDP with the ability of H₂O₂ self-generation, thermal responsiveness, and enhanced CDT effects for applications in cancer therapy.