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Background: Activating the cytosolic innate immune sensor, the cGAS-STING pathway, holds great promise for enhancing antitumor immunity, particularly in combination with immune checkpoint inhibitors (ICIs). However, the clinical application of STING agonists is often hindered by poor tumor accumulation, limited cellular uptake, and rapid clearance. To address these challenges, we developed a human serum albumin (HSA)-based nanoreactor system for the efficient delivery of the STING agonist SR-717, aiming to improve its antitumor efficacy. Methods: Using a biomineralization technique, we encapsulated SR-717 within HSA nanocages to form SH-NPs. These nanoparticles were characterized in terms of size, stability, and cellular uptake, and their ability to activate the STING pathway was assessed in both in vitro and in vivo models, including freshly isolated human renal tumor tissues. In vivo antitumor efficacy was evaluated in a murine renal tumor model, and immune responses were measured. Results: SH-NPs exhibited enhanced stability, efficient cellular uptake, and superior tumor accumulation compared to free SR-717. They robustly activated the STING pathway, as evidenced by increased phosphorylation of TBK1 and IRF3, along with elevated IFN-β production. Additionally, SH-NPs reshaped the immunosuppressive tumor microenvironment, promoting T-cell-mediated immunity and improving the therapeutic efficacy of checkpoint blockade in murine models. The validation in human renal tumor tissues further highlighted their potential for clinical translation. Importantly, SH-NPs were well tolerated with minimal systemic toxicity. Conclusions: This study underscores the potential of HSA-based nanoparticles for the targeted delivery of STING agonists, effectively enhancing antitumor immunity and improving cancer immunotherapy outcomes. SH-NPs offer a promising solution to the limitations of current STING agonists in clinical settings. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) contributes to more than 90% of all oral malignancies, yet the performance of traditional treatments is impeded by limited therapeutic effects and substantial side effects. In this work, we report a combinational treatment strategy based on tumor exosome-based nanoparticles co-formulating a photosensitizer (Indocyanine green) and a tyrosine kinase inhibitor (Gefitinib) (IG@EXOs) for boosting antitumor efficiency against OSCC through synergistic phototherapy-molecular targeted therapy. The IG@EXOs generate distinct photothermal/photodynamic effects through enhanced photothermal conversion efficiency and ROS generation, respectively. In vivo, the IG@EXOs efficiently accumulate in the tumor and penetrate deeply to the center of the tumor due to passive and homologous targeting. The phototherapy effects of IG@EXOs not only directly induce potent cancer cell damage but also promote the release and cytoplasmic translocation of Gefitinib for achieving significant inhibition of cell proliferation and tumor angiogenesis, eventually resulting in efficient tumor ablation and lymphatic metastasis inhibition through the synergistic phototherapy-molecular targeted therapy. We envision that the encouraging performances of IG@EXOs against cancer pave a new avenue for their future application in clinical OSCC treatment. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. Hyperthermia is widely used in combination with chemotherapy and radiotherapy to enhance therapeutic efficacy in NPC treatment, but the underlying anti-tumor mechanisms of hyperthermia remain unclear. Complement C3 has been reported to participate in the activation of immune system in the tumor microenvironment, leading to tumor growth inhibition. In this study, we aimed to explore the effect and mechanisms of hyperthermia and investigate the functional role of complement C3 in NPC hyperthermia therapy (HT). The serum levels of complement C3 before and after hyperthermia therapy in patients with NPC were analyzed. NPC cell lines SUNE1 and HONE1 were used for in vitro experiment to evaluate the function of complement C3 and HT on cell proliferation and apoptosis. SUNE1 xenograft mouse model was established and tumor-bearing mice were treated in water bath at a constant temperature of 43°C. Tumor samples were collected at different time points to verify the expression of complement C3 by immunohistochemical staining and western blot. The differential expressed genes after hyperthermia were analyzed by using RNA sequencing. We found that complement could enhance hyperthermia effect on suppressing proliferation and promoting apoptosis of tumor cells in NPC. Hyperthermia decreased the mRNA expression of complement C3 in tumor cells, but promoted the aggregation and activation circulating C3 in NPC tumor tissue. By using in vitro hyperthermia-treated NPC cell lines and SUNE1 xenograft tumor-bearing mice, we found that the expression of heat shock protein 5 (HSPA5) was significantly upregulated. Knockdown of HSPA5 abrogated the anti-tumor effect of hyperthermia. Moreover, we demonstrated that hyperthermia downregulated CD55 expression via HSPA5/NFκB (P65) signaling and activated complement cascade. Our findings suggest that therapeutic hyperthermia regulates complement C3 activation and suppresses tumor development via HSPA5/NFκB/CD55 pathway in NPC. Complement was involved in the anti-tumor effect of hyperthermia in vitro. Hyperthermia markedly increased the expression of heat shock protein 5 (HSPA5) and decreased the expression of CD55 which regulated the activation of complement C3 and complement cascade. Activation of HSPA5/NFκB (P65) signaling pathway resulted in a decrease in CD55 expression. [ABSTRACT FROM AUTHOR]

In this work, the flow field of an autorotating rotor in a water tunnel with various pitches and shaft backward angles was investigated via particle image velocimetry (PIV). The experiments were carried out on a free-rotating two-bladed single rotor. Computational Fluid Dynamics (CFD) based on moving overset grids were developed to study the hydrodynamic characteristics of an underwater autorotating rotor. The simulation results are in good agreement with the test results. The thrust and thrust coefficient of the underwater autorotating rotor were calculated by CFD simulation under different situations. The research demonstrates that rotational speed and thrust have a significant positive correlation with water velocity, pitch, and shaft back angle. In particular, the thrust coefficient scarcely varies with the shaft backward angle. An underwater autorotation rotor with a thin airfoil, negative torque, and a suitable number of blades can increase the thrust and thrust coefficient. The investigation is of significance in enriching the autorotation theory of rotors and helping to develop underwater autorotating rotors. [ABSTRACT FROM AUTHOR]