The nanocatalytic activity of nanozymes provides a vision for tumor treatment. However, the glutathione (GSH)-related antioxidant defense system (ADS) formed on the basis of excessive GSH in the tumor microenvironment limits its catalytic activity. Here, dendritic mesoporous silica nanoparticles (DMSNs) were employed as nanocarrier; ultrasmall Fe3O4 nanoparticles, Mn2+ ions, and glutaminase inhibitor Telaglenastat (CB-839) were subsequently integrated into large mesopores of DMSNs, forming DMSN/Fe3O4–Mn@CB-839 (DFMC) nanomedicine. This nanomedicine exhibits peroxidase mimicking activities under acidic conditions, which catalyzes the decomposition of hydrogen peroxide (H2O2) into hydroxyl radical (•OH). This also promotes the formation of lipid peroxides, which is required for ferroptosis. Furthermore, this nanomedicine can effectively deplete the existing GSH, thereby enhancing reactive oxygen species (ROS)-mediated tumor catalytic therapy. Moreover, the introduced CB-839 blocks the endogenous synthesis of GSH, further enhancing GSH depletion performance, which reduces the excretion of oxaliplatin (GSH-related resistance) from tumor cells, thereby restoring the chemical sensitivity of oxaliplatin. The dual GSH depletion property significantly weakens the GSH-related ADS and restores the chemical sensitivity of oxaliplatin, leading to the high DFMC-induced apoptosis and ferroptosis of tumor cells. Our developed nanomedicine based on integrated nanotechnology and clinical drug may aid the development of tumor treatment.

The immunosuppression and immune escape of current immunotherapy result in low efficacy, and ferroptosis is greatly restricted by the low reactive oxygen species (ROS) production efficiency. Here, for the first time a “closed‐loop” therapy based on photothermal enhancement of ferroptosis and immunotherapy stimulated by each other on a multifunctional nanoplatform is reported. This platform is composed of copper silicate and iron silicate mesoporous hollow nanospheres, followed by in situ growth of Au nanoparticles and loading of an immune adjuvant resiquimod R848. The laser irradiation‐mediated heat and the introduction of copper ions significantly enhance ROS generation, leading to the simultaneous depletion of glutathione peroxidase 4 (GPX4) and glutathione (GSH). The onset of ferroptosis in tumor cells is thus enhanced and an immune response with immunogenic cell death (ICD) is triggered, promoting the dendritic cells (DCs) maturation and T cell infiltration. Interferon γ (IFN‐γ) released from CD8+ T cells downregulates the expression of SLC7A11 and GPX4, which in turn enhances ferroptosis expression, thus constituting a “closed‐Loop” therapy. Importantly, this system is effective in both killing the primary tumor and inhibiting tumor metastasis. The proposed “closed‐loop” therapeutic strategy may provide a guidance for the design of future antitumor nanoplatforms.

Increasing evidence indicated that long noncoding RNAs (lncRNA) play critical roles in the progression of multiple cancers and that dysregulation of lncRNA promotes tumor progression. However, the function and underlying mechanism of lncRNA DLEU2 in biological behaviors of NSCLC cells are still largely unknown. Our studies confirmed that lncRNA DLEU2 was highly expressed in NSCLC tissues and cell lines, which was correlated with shorter overall survival in NSCLC patients. In vitro, knockdown of lncRNA DLEU2 inhibited proliferation, invasion, migration and induced apoptosis of both A549 and LLC cells; In vivo, it suppressed tumor growth and metastasis. lncRNA DLEU2 directly interacted with miR-30c-5p, which further targeted SOX9 and exerted oncogenic functions in NSCLC. Mechanistically, overexpression of lncRNA DLEU2 exhibits tumorigenic effects through downregulating the inhibitory effect of miR-30c-5p on SOX9 expression. In conclusion, Our finding confirmed that lncRNA DLEU2 as a novel oncogenic in NSCLC, which provide a potential novel diagnostic and therapeutic target for NSCLC.

Mild photothermal therapy (PTT, <45 °C) can prevent tumor metastasis and heat damage to normal tissue, compared with traditional PTT (>50 °C). However, its therapeutic efficacy is limited owing to the hypoxic tumor environment and tumor thermoresistance owing to the overproduction of heat shock proteins (HSPs). Herein, a near‐infrared (NIR)‐triggered theranostic nanoplatform (GA‐PB@MONs@LA) is designed for synergistic mild PTT and enhanced Fenton nanocatalytic therapy against hypoxic tumors. The nanoplatform is fabricated by the confined formation of Prussian blue (PB) nanoparticles in mesoporous organosilica nanoparticles (MONs), followed by the loading of gambogic acid (GA), an HSP90 inhibitor, and coating with thermo‐sensitive lauric acid (LA). Upon NIR irradiation, the photothermal effect (44 °C) of PB not only induces apoptosis of tumor cells but also triggers the on‐demand release of GA, inhibiting the production of HSP90. Moreover, the delivered heat simultaneously enhances the catalase‐like and Fenton activity of PB@MONs@LA in an acidic tumor microenvironment, relieving the tumor hypoxia and promoting the generation of highly toxic •OH. In addition, the nanoplatform enables magnetic resonance/photoacoustic dual‐modal imaging. Thus, this study describes a distinctive paradigm for the development of NIR‐triggered theranostic nanoplatforms for enhanced cancer therapy.

Semimetallic nanomaterials as photothermal agents for bioimaging and cancer therapy have attracted tremendous interest. However, the poor photothermal stability, low biocompatibility, and single component limit their therapeutic efficiency in cancer treatment. Here, manganesedoped VSe 2 semimetallic nanosheets were prepared and subsequently modified with chitosan (named VSe 2 /Mn-CS NSs) for combined enzyme catalytic and photothermal therapy. VSe 2 /Mn-CS NSs show high photothermal property with a photothermal conversion efficiency of 34.61% upon 808 nm near-infrared laser irradiation. In the tumor microenvironment, VSe 2 /Mn-CS NSs can convert endogenous H 2 O 2 into lethal hydroxyl radicals (•OH) to induce cancer cell apoptosis. The interaction between glutathione (GSH) and Se−Se bonds in VSe 2 /Mn-CS NSs results in the depletion of GSH level, and the valence states transition of manganese ions is also beneficial for the GSH consumption. This dual depletion of GSH markedly enhances the peroxidase (POD) activity, leading to the high •OH production and the improved therapeutic effect. What is more, the T 1 -weighted magnetic resonance and photoacoustic imaging endow VSe 2 /Mn-CS NSs with the ability to guide and track the treatment process. Our study provides a research strategy for the application of semimetallic nanomaterials in cancer diagnosis and treatment.