Lung inflammation, injury, and fibrosis are interconnected facets of respiratory health. Damage to the inherent lung architecture and tissue scarring resulting from excessive extracellular matrix deposition are the most important characteristics of lung injury and fibrosis. Although the current treatment strategy like Pirfenidone and Nintedanib, is effective in slowing the disease progression, they do not offer a complete cure. To suppress inflammation and pulmonary fibrosis progression, a variety of phytochemical drugs (Polyphenols, alkaloids, terpenoids, and carotenoids) have been investigated in the last decade. The bare administration of phytochemical drugs results in lower efficacy due to their low bioavailability, non-specific release, and inadequate absorption in the lungs. With recent advancements in nanotechnology-based drug delivery systems, researchers are highlighting the advantages of phytochemical drug delivery through a nanomedicine approach, with enhanced lung targetability and efficacy. In this review, the role of phytochemical drugs and the current status of phytochemical delivery using various nanocarriers (Polymeric, lipid, inclusion complexes, metal-organic frameworks, hybrid, and lung targetable nanocarriers) for treating lung inflammation and fibrosis are presented.

Three-dimensional (3D) models to study human disease mechanisms have demonstrated that the third dimension is an essential component for neuronal maturation and function. However, 3D neuronal cell culture is challenging due to their ultra-soft nature and specific extracellular matrix (ECM) organization. This study presents a microfiber reinforcement approach, combining primary mouse spinal cord neurons (SCNs) in a purpose-adaptable hyaluronic-acid-based matrix with melt electrowritten (MEW) frames to study disease mechanisms. The importance of laminins (LNs) is evaluated, which are vital for neuronal adhesion and maturation. Astrocytes (ACs) are mandatory in brain development and function by secretion of signal molecules, maintaining ion homeostasis, clearing of neurotransmitters, and by actively modulating neuronal activity. Three combinations are compared (i) isolated primary SCN, (ii) SCN with ACs (SCN-AC) and (iii) SCN-AC and LNs (SCN-AC-LN). Multimodal analysis by comparing protein expression, dendrite length, complex mechanical properties, and network functionality via Ca2+-imaging allows validation of structural and functional neuronal network development. The suitability of the 3D model to study pathomechanisms is demonstrated for Stiff Person Syndrome (SPS). For the first time, functional impairment of spinal cord neurons by patient-derived autoantibodies characteristic for SPS is recapitulated in a 3D spinal cord model platform adaptable to other disease types.

Obesity has emerged as one of the most critical global health challenges.However, current anti-obesity pharmacotherapies are limited by suboptimal efficacy and significant side effects. White adipose tissue (WAT)browning may contribute to ameliorating obesity. In this study, a water-soluble lipophilic second near-infrared region (NIR-II) photothermal agent, CPDT-BBT-N (BTN), which specifically targets lipid droplets (LDs) and accumulates in adipocytes, was developed. Upon NIR irradiation, BTN induced a strong photothermal effect, enabling localized mild hyperthermia that specifically triggers white adipocyte browning with high efficiency and minimal off-target effects. WAT browning markedly accelerated the burning of the excessive fat accumulated in adipocytes. Notably, this intervention also showed systemic metabolic benefits. In high-fat diet (HFD)-induced obese mice, the BTN + NIR treatment attenuated weight gain by 20%, reduced subcutaneous WAT mass by 43%, and decreased visceral fat mass by 35%. Furthermore, it significantly reduced serum cholesterol (38%), triglycerides (30%), insulin (30%), and glucose levels (35%) while improving insulin sensitivity. Mechanistically, mild thermal stimulation promoted calcium influx in adipocytes, upregulating the expression of the thermogenic protein UCP1, enhancing mitochondrial oxidative respiration, and facilitating lipid catabolism. Together, these findings provide a novel and feasible strategy for effectively and safely managing obesity.

Uterine dysfunction arising from surgical procedures such as curettage and caesarean section often leads to adhesions, hyperplasia and fibrosis, undermining women's fertility and quality of life. Conventional pharmacological and physical therapies cannot fully restore uterine function. To overcome these limitations, we designed a composite, polysaccharide-coated silk nanofiber film as a staged scaffold to meet evolving healing demands. The hydrophilic polysaccharide layer provides early postoperative wet strength, conformability and physical isolation, while the underlying nanofibrous silk network mimics the extracellular matrix to support cell adhesion, proliferation and regeneration in later stages. In a rat model of severe uterine injury, implantation of this biodegradable film prevented postoperative adhesions and preserved reproductive capacity, achieving a fertility rate exceeding 80%. Mechanistically, the scaffold modulates the immune microenvironment by promoting M2 macrophage polarization, attenuating inflammation and accelerating tissue repair. It also upregulates angiogenic factors (VEGF-A, PDGF-BB), enhances type III collagen deposition and minimizes foreign-body reaction, collectively driving effective in situ uterine regeneration. Fabricated via aqueous electrospinning and mild coating, the scaffold is cost-effective, ecofriendly and readily scalable. As a biodegradable, staged platform tailored to dynamic uterine healing, this material offers a novel, versatile solution for clinical translation in uterine repair and broader regenerative-medicine applications.

The efficacy of cancer therapies is often limited by inefficient drug delivery due to the highly heterogeneous tumor microenvironment (TME) and various cellular resistances, such as uptake and lysosomal escape. To overcome these challenges, we designed and synthesized three integrated polyesters through BODIPY-initiated ring-opening block copolymerization, BSN1-BSN3, which incorporate an SN38 prodrug and a cationic positively charged ([12]aneN3) unit. The optimized polyester BSN3 was co-assembled with DOPE, DSPE-PEG-iRGD, and Bcl-2-siRNA into multifunctional nanoparticles, BSN3-DR/Bcl-2 siRNA NPs. This system achieves spatiotemporally controlled activation within tumors through iRGD-mediated targeting for enhanced cellular uptake, followed by 660nm light-triggered photochemical internalization (PCI) to enable lysosomal escape, as well as high GSH/esterase-triggered disassembly of NPs for sequential release of siRNA and SN38. The combination of Bcl-2 protein silencing, chemotherapy, and PDT led to significant tumor growth inhibition at 95% in vivo in HCT116 models, without observable systemic toxicity. This work not only presents a novel cascade-responsive combination strategy to overcome the limitations of monotherapy and physical combination of different therapeutic components but also offers valuable experimental evidence and theoretical support for the development of highly efficient and safe polymeric nanodrugs.

Mandibular bone defects, especially critical-sized ones, are a major challenge in oral and maxillofacial surgery. Electrical stimulation (ES) enhances bone repair, but its underlying mechanism remains elusive. This study presents a masticatory-driven piezoelectric hydrogel that converts chewing motions into endogenous-like ES, triggering on-demand NPY condensate release to enhance regeneration, validated in rat critical-sized defect models. NPY as a key mediator is identified: ES triggers its phase transition to activate osteogenic signaling. The engineered hydrogel generates >20mVcm-1 (exceeding the ≥2mVcm-1 threshold for NPY liquid-liquid phase separation, LLPS) under physiological chewing. ES induces NPY conformational rearrangement (N-terminus buried) to activate Y2 receptors (Y2R) on periodontal ligand-derived stromal cells (PDLSCs). Mechanistically, ES plus NPY condensate promotes osteogenic differentiation of PDLSCs through pAKT-Runx2 signaling. In vitro, the hydrogel boosts PDLSCs osteogenesis by 2-fold (p < 0.001). In 4-week and 12-week rat mandibular bone defects, it yielded greater bone volume and higher density (p < 0.01) vs. controls, with Y2R-pAKT-RUNX2 activation confirmed. This self-powered strategy leverages mastication for targeted ES, offering a mechanism-driven solution that addresses current limitations and holds clinical promise.