Zhongjian Chen

Primary research hotspots for ferritin-based drug delivery systems. Created using the © 2023 BioRender.

Smart and efficient drug delivery is always desirable, especially for chronic diseases, such as psoriasis. We developed an ultraviolet B (UVB) light‐triggered scaffold, 1,4,2‐dioxazol‐5‐thione (DOT), for the controlled release of hydrogen sulfide (H ₂ S), a pivotal endogenous gaseous signaling molecule with promise for anti‐inflammatory and antioxidant therapies. In the DOT scaffold, the kinetics for H ₂ S release are efficiently tuned by fine‐adjusting the electronic properties. Upon photoirradiation, DOT releases carbonyl sulfide (COS), which is rapidly converted to H ₂ S by carbonic anhydrase (CA). Furthermore, the DOT platform is conjugated to the active pharmaceutical ingredient pterostilbene (PTE) to afford a hybrid prodrug, PTE‐DOT. Under UVB irradiation at 308 nm, a standard wavelength for psoriasis phototherapy, PTE‐DOT simultaneously released H ₂ S and PTE, thereby exerting combined anti‐inflammatory and antioxidant effects in vivo. In the psoriasis mouse model, PTE‐DOT effectively reduced epidermal thickening and hyperkeratosis, suppressed the production of key psoriatic inflammatory cytokines, and inhibited the differentiation of Th17 cells in the spleen. Thus, the photo‐controlled prodrug strategy provides a platform for designing smart drug delivery systems to ameliorate psoriasis‐like skin inflammation.

Objective: Belimumab has been proven to be effective for treating refractory lupus nephritis. However, the meaningful renal response is still far from satisfactory. This study sought to identify immunological biomarkers to stratify patients who are likely to benefit from belimumab therapy. Methods: We retrospectively reviewed the medical records of patients with refractory lupus nephritis who received 6 months belimumab treatment. Complete response (CR), partial response (PR) and no response (NR) were evaluated, and the predictors of CR were identified. Results: A total of 28 patients with refractory LN were enrolled. The proportions of CR, PR and NR at 6 months were 39.29%, 32.14% and 28.57%, respectively. The baseline CD19+B cell proportions were significantly higher in CR patients than those in non-CR patients (19.30% vs 10.72%, p<0.001). In the binary logistic regression, baseline CD19+B cell proportion was identified as a predictor of CR in both univariate analysis (OR 1.359, 95% CI 1.098 to 1.683, p=0.005) and exploratory multivariate analysis adjusting for 24-hour urinary protein (OR 1.349, 95% CI 1.092 to 1.665, p=0.005). Receiver operating characteristic showed that the cut-off level of CD19+B cell proportion was 15.12%, with a sensitivity of 90.90%, specificity of 88.20% and an area under curve of 0.888 (95% CI 0.759 to 1.000, p=0.001). Conclusion: Findings support the baseline CD19+B cell proportion could be used to predict CR to treatment with belimumab in refractory lupus nephritis patients.

Chronic diabetic wounds represent a significant therapeutic challenge, characterized by persistent inflammation, impaired angiogenesis, and defective efferocytosis. In this study, we demonstrate that stem cell-derived biomimetic apoptotic vesicles (AVs) are enriched with complement C1q-binding protein (C1qbp), and confirm that C1qbp is a key regulator for macrophage phagocytosis. These AVs potently enhanced macrophage efferocytic activity, promoted polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype, and reduced secretion of the pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Moreover, AVs stimulated angiogenesis and cell migration, thereby initiating a coordinated immune-mediated tissue regenerative program. Delivery of AVs via a GelMA hydrogel (AVs@GelMA) markedly accelerated wound healing in diabetic mice by inhibiting nuclear factor-κB (NF-κB)-driven inflammatory signaling and promoting vascularization and tissue remodeling. Collectively, our findings elucidate a three-phase mechanism of "efferocytosis-immunity-regeneration" and highlight C1qbp-enriched AVs as a promising precision therapeutic strategy for chronic diabetic wounds.

Tumor vaccines represent a promising strategy for mobilizing the immune system against malignancies, however, their efficacy is limited by poor antigen imm

Introduction: Psoriasis is a prevalent chronic inflammatory skin disease in which pattern recognition receptors, particularly the NLRP3 inflammasome, are increasingly implicated in disease pathogenesis. Solanum nigrum (SN) has been used in traditional and clinical practice for psoriasis treatment, but its therapeutic mechanisms and key active constituents remain unclear. This study investigated the anti-psoriatic mechanisms of SN and identified its major bioactive component. Methods: NLRP3 inflammasome activation in psoriasis was evaluated using public transcriptomic datasets and clinical skin biopsies. The therapeutic effects of SN were assessed in imiquimod-induced primary and relapse psoriasis-like dermatitis models. Bulk RNA sequencing of lesional skin was performed to identify SN-regulated pathways. SN was chemically characterized by UPLC–MS, and candidate active compounds were prioritized by molecular docking and molecular dynamics simulation. Results: NLRP3 inflammasome activation was consistently elevated in psoriatic lesions in both public datasets and clinical specimens. SN markedly alleviated disease severity in primary and relapse models, reduced keratinocyte hyperproliferation, and lowered systemic inflammatory cytokine levels. Transcriptomic analysis showed that SN mainly modulated PRR/NLR-related signaling pathways. Mechanistically, SN inhibited NLRP3 inflammasome activation and decreased IL-1β and IL-18 production. Integrated chemical, biological, and computational analyses identified trigonelline as a major active constituent contributing to the anti-psoriatic effects of SN. Discussion: SN ameliorates psoriasis-like dermatitis primarily through suppression of NLRP3 inflammasome signaling, with trigonelline identified as a key contributory active component. These findings provide mechanistic support for the therapeutic application of SN in psoriasis.

Despite advances in immunotherapy, the efficacy against melanoma remains limited in aged individuals, primarily due to diminished dendritic cell (DC) function and an immunosuppressive tumor microenvironment. To address this, we report a chemically engineered “tumor ghost” nanovaccine (dMVac) constructed through a biomimetic synthesis strategy. The core nanovesicles are derived from separate melanoma cells subjected to hypochlorous acid oxidation and UVB radiation, respectively, enriching them with a broad spectrum of tumor antigens and endogenous damage‐associated molecular patterns. These nanovesicles are further functionalized via lipid‐insertion chemistry to co‐anchor the DC‐hyperactivating molecules: the oxidized phospholipid PGPC and cholesterol‐conjugated CpG oligonucleotide. This surface engineering enables efficient lymph node targeting and promotes synergistic DC activation. The resulting dMVac reverses age‐related DC dysfunction by enhancing their activation, migration, and IL‐1β secretion, thereby stimulating robust cytotoxic T‐cell responses and memory formation in aged mice. Moreover, dMVac synergizes with doxorubicin (DOX) and anti‐PD‐1 therapy to reprogram the immunosuppressive tumor microenvironment via enhanced antigen presentation and T‐cell infiltration, leading to significant suppression of tumor progression. This work demonstrates how rational chemical design of a bio‑hybrid nanovaccine can overcome age‐associated immune dysfunction, providing a versatile platform for cancer immunotherapy.

Despite advances in immunotherapy, the efficacy against melanoma remains limited in aged individuals, primarily due to diminished dendritic cell (DC) function and an immunosuppressive tumor microenvironment. To address this, we report a chemically engineered “tumor ghost” nanovaccine (dMVac) constructed through a biomimetic synthesis strategy. The core nanovesicles are derived from separate melanoma cells subjected to hypochlorous acid oxidation and UVB radiation, respectively, enriching them with a broad spectrum of tumor antigens and endogenous damage‐associated molecular patterns. These nanovesicles are further functionalized via lipid‐insertion chemistry to co‐anchor the DC‐hyperactivating molecules: the oxidized phospholipid PGPC and cholesterol‐conjugated CpG oligonucleotide. This surface engineering enables efficient lymph node targeting and promotes synergistic DC activation. The resulting dMVac reverses age‐related DC dysfunction by enhancing their activation, migration, and IL‐1β secretion, thereby stimulating robust cytotoxic T‐cell responses and memory formation in aged mice. Moreover, dMVac synergizes with doxorubicin (DOX) and anti‐PD‐1 therapy to reprogram the immunosuppressive tumor microenvironment via enhanced antigen presentation and T‐cell infiltration, leading to significant suppression of tumor progression. This work demonstrates how rational chemical design of a bio‑hybrid nanovaccine can overcome age‐associated immune dysfunction, providing a versatile platform for cancer immunotherapy.