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

Nanomedicine‐Enabled/Augmented Cell Pyroptosis for Efficient Tumor Nanotherapy

“…[22] The ROS level in CA-Re treated normoxic cells was negligible in the darkness, but ROS generation was significantly elevated in a concentrationdependent manner under near infrared (NIR) irradiation (Figure 3b). As shown in SEM observation, the CA-Re treating tumor cells exhibited pyroptotic features with fried egg cells with flat cytoplasm and intact nuclei located on the main plane, which was visibly different from the control cells and apoptotic cells treated CA-Re GSDMD 4T-1 cells PDT triggered immunogenic pyroptosis to enhance DCs maturation and systemic immune effects [22] Magnetic fluid hyperthermia Gastrin-MNPs INR1G9-CCK2R cells Increase the temperature and promote cytotoxic free radical generation for pyroptosis [23] TMZ/Fe-TSL GSDMD U87 and U251 cells Elevate the temperature in tumor site for inducing pyroptosis under the AMF irradiation [24] Photonic hyperthermia BNP GSDME 4T-1 cells Regulate immunosuppressed TME and improve the immune responses [26] Chemodynamic therapy VTPA GSDMD 4T-1 cells Intracellular release of Mn ions and iron oxide nanoparticles to produce abundant ROS through Fenton-like reactions [30] FeSO 4 GSDME A375 Iron-induced CDT for oligomerization of Tom20 for pyroptosis [31] Starvation therapy PICsomes 4T-1 cells Glucose depletion amplified the oxidative stress in cascade reaction to increase pyroptotic efficiency [33] Ion-interference therapy Lip-MOF GSDMD HeLa cells Increase the intracellular Fe ion concentration to trigger pyroptosis [36] NaCl nanocrystals GSDMD HepG2 cells GSH-responsive explosive ion to induce pyroptosis [39] CaNMs GSDME 4T-1 cells Calcium overload-inducing pyroptosis to improve DCs maturation and systemic immune effects [43] Chemotherapy Lipo-DDP GSDME 4T-1 cells Improve the immune response of chemotherapy by epigenetic-based pyroptosis [46] As by dimethyl sulfoxide (DMSO) (Figure 3c). The expressions of pyroptotic markers (caspase-1 and GSDMD) and the levels of immune cells (DCs, CD4 + , and CD8 + ) were both visibly increased in the CA-Re under light irradiation, as detected by western blot and ELISA, respectively.…”

“…Reproduced with permission. [24] Copyright 2022, Elsevier. The level of GSDME N-terminals, caspase-3, and CD4 + T cells after different treatments, respectively.…”

“…Coincidentally, to enhance the tumor accumulation, the temozolomide and magnetic Fe 3 O 4 were encapsulated by the temperature‐sensitive liposomes (TMZ/Fe‐TSL) to heat the local glioblastoma (GBM) cells to about 42 °C without damaging surrounding normal tissues in the presence of AMF (Figure 4b ). [ 24 ] The heating temperature promotes transient opening of the blood–brain barrier (BBB), facilitates the on‐demand drug release, and improves the generation of free radicals. The cell viability treated by TMZ/Fe‐TSL + AMF demonstrated the enhanced cell death rates in both U251 cells and U87 cells (56.13 ± 6.124% and 48.35 ± 0.495%).…”

“…b) Schematic representation of TMZ/Fe-TSL and pyroptosisrelated protein expressions in U87 cells after different treatments. Reproduced with permission [24]. Copyright 2022, Elsevier.…”

Intelligent Nanoparticles With pH-Sensitive Co-Delivery of Temozolomide and siEGFR to Ameliorate Glioma Therapy

“…Presently, temozolomide (TMZ), as a standard chemotherapeutic treatment for GBM, has shown confirmed success in improving the survival rate of patients suffering from this disease ( Ziu et al, 2015 ; Bi et al, 2018 ). However, TMZ’s clinical effectiveness is restricted by the following problems: 1) the acquired drug resistance of glioma cells to TMZ during chemotherapy ( Jiapaer et al, 2018 ), 2) damage to normal cells is caused by the indiscriminate attack on DNA ( Kim et al, 2015 ), and 3) due to the blood–brain barrier (BBB) preventing orally administered or intravenously administered TMZ from entering the brain; thus, the effectiveness of TMZ as an antiglioma treatment is greatly reduced ( Yao et al, 2022 ). Although the BBB restriction and the indiscriminate attack on DNA could be resolved by nanoparticles (NPs) as vehicles to targeted delivery of TMZ ( Cheng et al, 2021 ), drug resistance remains a huge challenge for TMZ to perform its best function ( Lee, 2016 ).…”