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Neuroblastoma(NB) is a common childhood solid tumor, and most patients in the high-risk group with MYCN gene amplification have a poor prognosis. Inhibition of bromodomain and extra terminal (BET) proteins has shown considerable promise in the investigation of MYCN-driven malignancies in recent years. MZ1 is a novel BET inhibitor that employs proteolytic-targeting chimera (PROTAC) technology for proteasomal degradation of target proteins and has shown excellent effects in some tumors, but its role in neuroblastoma remains poorly understood. Herein, we observed that MZ1 suppressed MYC-amplified NB cell proliferation and normal cell cycle, while simultaneously boosting cell apoptosis. MZ1 also provides a significant therapeutic impact in vivo. Mechanistically, MZ1 exhibits anti-tumor effect in NB cells by suppressing the expression of N-Myc or C-Myc as well as the MAPK signaling pathway. Overall, our data imply that MZ1 might be exploited as a possible therapeutic method for NB therapy.

Over last decades, the complexity and variability of hepatocellular carcinoma (HCC) has significantly interfered with the effectiveness of traditional treatment, and has gradually become a main obstacle and bottleneck for HCC therapy. In order to explore the innovative therapeutic strategy to further improve the cancer diagnosis and treatment, we herein proposed a thermal-induced magnetic nanosystem with good biocompatibility that therapeutic cargo controllable release relies on 808 nm laser irradiation. This nanosystem was designed by co-loaded the manganese-doped magnetic nanoparticles and photosensitizer indocyanine green into the matrix of temperature sensitive polymer, with further capturing negatively charged YAP1 siRNA on the surface, to finally obtain the heat-induced manganese-doped magnetic nanocarriers (HMM-siRNA NCs). Our study found that the photosensitizer on the exposure of 808 nm laser irradiation could generate continuous heat to rupture the thermal-sensitive polymer matrix, that controllable release the embedded ICG and Mn0.8Fe2.2O4 NPs for NIR/MR imaging, ICG-mediated heat and ROS could induce the thermal expansion and rupture of HMM-siRNA NCs, causing the evident thermal swelling of lysosomes to induce the cell apoptosis. Besides, YAP1 siRNA can decrease the YAP1 expression in HCC down to approximately 35%, reducing the cell proliferation and migration. Such NIR/MRI guided low-temperature PTT and siRNA-mediated gene therapy strategy lead to tumor cell death by using various and complementary approach, thereby achieving controllable and effective comprehensive treatment in the presence of 808 nm laser irradiation. Our designed delivery complex can accomplish the precise cancer treatment on the tumor site by responding to the external 808 nm laser, and its non-toxic metabolites demonstrate the excellent biocompability for extensive use either anti-cancer therapy or various disease from clinical research.