TMZ magnetic temperature-sensitive liposomes-mediated magnetothermal chemotherapy induces pyroptosis in glioblastoma.

Glioblastoma (GBM) is the most fatal and common type of primary malignant tumors in central nervous system. Chemotherapy drugs are difficult to reach the encephalic region effectively due to blood-brain barrier (BBB), but functional nanoparticle drug carriers can help to solve the problem. Herein, we developed a controllable drug carrier called temozolomide magnetic temperature-sensitive liposomes (TMZ/Fe-TSL) to investigate its feasibility and molecular mechanisms on GBM. Our research found TMZ/Fe-TSL exposed to alternating magnetic field (AMF) could induce significantly GBM cell death and promote the production of ROS. It also showed that the expression of NLRP3, CASP1 and N-GSDMD was upregulated compared to the control group, while the expression of CASP3 showed a reverse change. The results indicated that TMZ/Fe-TSL exposed to the AMF was capable of inducing GBM cells death. And the way and mechanisms of cell death may involve in ROS and pyroptosis, but not apoptosis.

Preparation and Characterization of Fe3O4@MTX Magnetic Nanoparticles for Thermochemotherapy of Primary Central Nervous System Lymphoma in vitro and in vivo.

BACKGROUND: Primary central nervous system lymphomas (PCNSL) are extranodal malignant non-Hodgkin lymphomas (NHL) that arise exclusively in central nervous system (CNS). Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype. PURPOSE: To evaluate whether nano drug-loading system-mediated magnetic-targeted thermochemotherapy could produce a better therapeutic effect than single chemotherapy while reducing the use of chemotherapeutic drugs. METHODS: Six groups (control, Fe3O4, MTX, Fe3O4@MTX, Fe3O4 with hyperthermia and Fe3O4@MTX with hyperthermia) were set. Tumor cell apoptosis in each treatment group was detected by flow cytometry. Apoptosis-related gene expressions Caspase-3, Bax and Bcl-2 were detected by qPCR and Western blot; intracranial tumor model of PCNSL was established by intracranial injection of OCI-LY18 tumor cells into BALB/c-Nude mice. Magnetic resonance imaging (MRI) was used to monitor tumor progression and H&E staining was used to observe pathological changes of the tumor tissue. RESULTS: In vitro, compared with chemotherapy alone, apoptosis rate of Fe3O4@MTX mediated thermochemotherapy group was significantly increased, and expression of apoptosis-inducing gene Caspase-3 and Bax were significantly upregulated in OCI-LY18 cells, while expression of apoptosis-inhibiting Bcl-2 gene was significantly downregulated. In vivo, MRI showed successful generation of intracranial tumor, and tumor volume was significantly smaller in combined thermochemotherapy group than in single chemotherapy group. H&E staining result of tumor tissues in each group was consistent with MRI; tumor cells were significantly reduced in thermochemotherapy group. Expression of apoptosis-related gene Caspase-3 and Bax were significantly upregulated in tumor tissues, while expression of Bcl-2 gene was significantly downregulated. CONCLUSION: These results demonstrated in vivo and in vitro that the combined thermochemotherapy of Fe3O4@MTX MNPs was superior to the single MTX chemotherapy with less dosage, which may promote apoptosis of DLBCL cells through the mitochondrial apoptotic pathway and provided a new way for the treatment of PCNSL.