The incorporation of new modalities into chemotherapy greatly enhances the anticancer efficacy combining the merits of each treatment, showing promising potentials in clinical translations. Herein, a hybrid nanomedicine (Au/FeMOF@CPT NPs) is fabricated using metal–organic framework (MOF) nanoparticles and gold nanoparticles (Au NPs) as building blocks for cancer chemo/chemodynamic therapy. MOF NPs are used as vehicles to encapsulate camptothecin (CPT), and the hybridization by Au NPs greatly improves the stability of the nanomedicine in a physiological environment. Triggered by the high concentration of phosphate inside the cancer cells, Au/FeMOF@CPT NPs effectively collapse after internalization, resulting in the complete drug release and activation of the cascade catalytic reactions. The intracellular glucose can be oxidized by Au NPs to produce hydrogen dioxide, which is further utilized as chemical fuel for the Fenton reaction, thus realizing the synergistic anticancer efficacy. Benefitting from the enhanced permeability and retention effect and sophisticated fabrications, the blood circulation time and tumor accumulation of Au/FeMOF@CPT NPs are significantly increased. In vivo results demonstrate that the combination of chemotherapy and chemodynamic therapy effectively suppresses the tumor growth, meantime the systemic toxicity of this nanomedicine is greatly avoided.

Optical imaging for biological applications is in need of more sensitive tool. Persistent luminescent nanophosphors enable highly sensitive in vivo optical detection and almost completely avoid tissue autofluorescence. Nevertheless, the actual persistent luminescent nanophosphors necessitate ex vivo activation before systemic operation, which severely restricted the use of long-term imaging in vivo. Hence, we introduced a novel generation of optical nanophosphors, based on (ZnSiO:Mn):Y, Yb, Tm upconverting persistent luminescent nanophosphors; these nanophosphors can be excited in vivo through living tissues by highly penetrating near-infrared light. We can trace labeled tumor therapeutic macrophages in vivo after endocytosing these nanophosphors in vitro and follow macrophages biodistribution by a simple whole animal optical detection. These nanophosphors will open novel potentials for cell therapy research and for a variety of applications in diagnosis in vivo.

Purpose: The purpose of this study was to construct a novel risk scoring model with prognostic value that could elucidate tumor immune microenvironment of hepatocellular carcinoma (HCC).Samples and methods: Data were obtained through The Cancer Genome Atlas (TCGA) database. Univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) analysis, and multivariate Cox analysis were carried out to screen for glycolysis-related long noncoding RNAs (lncRNAs) that could provide prognostic value. Finally, we established a risk score model to describe the characteristics of the model and verify its prediction accuracy. The receiver operating characteristic (ROC) curves of 1, 3, and 5 years of overall survival (OS) were depicted with risk score and some clinical features. ESTIMATE algorithm, single-sample gene set enrichment analysis (ssGSEA), and CIBERSORT analysis were employed to reveal the characteristics of tumor immune microenvironment in HCC. The nomogram was drawn by screening indicators with high prognostic accuracy. The correlation of risk signature with immune infiltration and immune checkpoint blockade (ICB) therapy was analyzed. After enrichment of related genes, active behaviors and pathways in high-risk groups were identified and lncRNAs related to poor prognosis were validated in vitro. Finally, the impact of MIR4435-2HG upon ICB treatment was uncovered.Results: After screening through multiple steps, four glycolysis-related lncRNAs were obtained. The risk score constructed with the four lncRNAs was found to significantly correlate with prognosis of samples. From the ROC curve of samples with 1, 3, and 5 years of OS, two indicators were identified with high prognostic accuracy and were used to draw a nomogram. Besides, the risk score significantly correlated with immune score, immune-related signature, infiltrating immune cells (i.e. B cells, etc.), and ICB key molecules (i.e. CTLA4,etc.). Gene enrichment analysis indicated that multiple biological behaviors and pathways were active in the high-risk group. In vitro validation results showed that MIR4435-2HG was highly expressed in the two cell lines, which had a significant impact on the OS of samples. Finally, we corroborated that MIR4435-2HG had intimate relationship with ICB therapy in hepatocellular carcinoma.Conclusion: We elucidated the crucial role of risk signature in immune cell infiltration and immunotherapy, which might contribute to clinical strategies and clinical outcome prediction of HCC.

Tumor-associated macrophages are highly versatile effector cells that have been used to kill tumor cells. Herein, the macrophages as cell-based biocarriers are used for the targeted delivery of photothermal reagents for promoting the efficiency of killing tumor cells by activating the anti-tumor immune response and photothermal therapy (PTT). In this design, macrophages cause the phagocytosis of tumor cells and activate the anti-tumor immune response by secreting plenty of cytokines. Meanwhile, to improve the tumor-killing effect and track the collaborative therapy system in vivo, a novel nanoplatform based on tungsten oxide (W18O49, WO) nanoparticles and fluorescent dyes loaded in polylactic-co-glycolic acid (PLGA) for PTT has been successfully constructed. Subsequently, the nanoparticles are swallowed by macrophages acting as cell-based biocarriers to target the tumor and promote solid tumor ablation in vivo in animal experiments. This system is expected to bring a huge application potential in the visually guided dual-modal therapeutic platform for tumor targeting therapy in vivo.

Systemic chemotherapy for oral squamous cell carcinoma (OSCC) is associated with multidrug resistance and systemic adverse effects. Cobalt‐ferrocene metal–organic framework (Co‐Fc) is a nanoparticle synthetized by ferrocene and cobalt with a stronger Fenton reaction that can locally generate hydroxyl radical and effectively kill tumors. However, tumor cells can remove exogenous substances through autophagy activity to maintain the internal environment homeostasis. Herein, Co‐Fc loaded with the classical autophagy inhibitor hydroxychloroquine (HCQ) to construct Co‐Fc@HCQ nanoparticles is synthetized. The ferrocene in Co‐Fc catalyzes the production of endogenous reactive oxygen species (ROS) through the Fenton reaction. The presence of HCQ inhibits the fusion of autophagy vesicles with lysosomes and reduces the scavenging of ROS. In addition, to enhance the tumor targeting effect of Co‐Fc@HCQ nanoparticles, oral cancer cell membranes (CM) are extracted from CAL‐27 cell line to construct CM@Co‐Fc@HCQ nanoparticles with good homologous targeting and immune escape effects. The results prove the good tumor targeting, biosafety as well as the therapeutic effect of CM@Co‐Fc@HCQ. In conclusion, via specific tumor targeting and local autophagy‐conducted ROS boosting, CM@Co‐Fc@HCQ nanoparticles, a smart local delivery chemo‐dynamic substance, provide a promising approach for effectively treating OSCC.