Psoriasis is a prevalent chronic immune-mediated skin disease characterized by excessive reactive oxygen species (ROS), immune imbalance, and inflammatory infiltration. Traditional single-target therapies often fail to achieve long-term remission. Here, we developed a multifunctional injectable hydrogel (JK&CM@HG) that integrated nanozyme-mediated antioxidant activity with hydrogen sulfide (H₂S) gas therapy for effective psoriasis treatment. The hydrogel exhibited good inject ability and tissue adhesion. Cerium-based metal-organic framework (Ce-MOF) nanozyme (CM) mimicked superoxide dismutase (SOD) and catalase (CAT), and scavenged superoxide anions (O₂^·−) and hydrogen peroxide (H₂O₂) to reduce oxidative stress. Meanwhile, the H₂S donor JK-1 (JK) releases H₂S in response to the acidic microenvironment, promoting macrophage polarization from M1 to M2, enhancing angiogenesis, and inhibiting abnormal keratinocyte proliferation. In vivo results showed that the hydrogel markedly alleviates erythema, reduces epidermal thickness, and restores near-normal architecture. Overall, JK&CM@HG achieved multi-target microenvironment modulation through synergistic ROS scavenging and H₂S therapy, effectively suppressing inflammation and promoting repair, offering a promising materials-design strategy for psoriasis management.

Poor tumor penetration is a significant challenge for using nanoliposome-based chemotherapy for triple-negative breast cancer (TNBC). Recently, a milieu of biological cues downregulating tumor stroma has been associated with biological metal ions, primarily such as Mn²⁺. Inspired by this, we hypothesized that Mn²⁺ could serve as a functional component in designing an alternative modulator for the tumor stroma microenvironment by reducing its extracellular matrix, further decreasing its stromal density. Herein, we presented a novel extracellular matrix (ECM) depleter within a tumor involving manganese-based mineralization materials that primed inhibition of the extracellular matrix of cancer cells, demonstrating a facile strategy for improving drug penetration, delivery and therapy efficiency of the doxorubicin-loaded liposome nanoparticles (Dox-LNP). As a result, the manganese mimetic mineralization material, manganese phosphate (MnP), demonstrated controlled biodegradation and biocompatibility within tumor microenvironments. The release of Mn²⁺ from MnP within the cell lysosome or tumor microenvironment inhibited TGF-β expression and its downstream profibrotic signaling pathways, thereby reducing the tumor stroma density by suppressing the expression of α-smooth actin (α-SMA) and collagen I (COL-I), and inducing tumor stromal disruption both in vitro and in vivo. The typical nanomedicines, Dox-LNP, were subsequently used to check their penetration. The MnP pretreated tumor could significantly improve tumor penetration and accumulation of Dox-LNP, which demonstrated a significant improvement in the treatment of TNBC. These achievements proposed a successful tumor stromal regulation material involving manganese mineralization for priming tumor stromal depletion in situ by inhibiting the TGF-β and associated proteins, representing an alternative materials strategy to substitute biotechnology for stromal reduction, which may further represent a great potential of nanomedicine-based cancer therapy.