Metal–Organic Framework-Based Nano-Activators Facilitating Microwave Combined Therapy via a Divide-and-Conquer Tactic for Triple-Negative Breast Cancer

Aiming at the clinical problems of high recurrence and metastasis rate of triple-negative breast cancer, a divide-and-conquer tactic is developed. The designed nanoactivators enhance microwave thermo-dynamic-chemotherapy to efficiently kill primary tumors, simultaneously ameliorate the immunosuppressive microenvironment, activate the tumor infiltration of T lymphocytes, and enhance the accumulation and penetration of PD-1/PD-L1 immune agents, ultimately boosting the efficacy of immune checkpoint blocking therapy to achieve efficient inhibition of distal tumors and metastases. Metal-organic framework (MOF)-based MPPT nano-activator is synthesized by packaging chemotherapeutic drug Pyrotinib and immunosuppressant PD-1/PD-L1 inhibitor 2 into MnCa-MOF and then coupling target molecule triphenylphosphine, which significantly improved the accumulation and penetration of Pyrotinib and immunosuppressant in tumors. In addition to the combined treatment of microwave thermo-dynamic-chemotherapy under microwave irradiation, Mn2+ in the nano-activator comprehensively promotes the cGAS-STING pathway to activate innate immunity, microwave therapy, and hypoxia relief are combined to ameliorate the tumor immunosuppressive microenvironment. The released Pyrotinib down-regulates epidermal growth factor receptor and its downstream pathways PI3K/AKT/mTOR and MAPK/ERK signaling pathways to maximize the therapeutic effect of immune checkpoint blocking, which helps to enhance the antitumor efficacy and promote long-term memory immunity. This nano-activator offers a generally promising paradigm for existing clinical triple-negative breast cancer treatment through a divide-and-conquer strategy

Reversal of Cisplatin Resistance in Ovarian Cancer by the Multitargeted Nanodrug Delivery System Tf-Mn-MOF@Nira@CDDP

Cisplatin (CDDP) is a widely used chemotherapeutic drug with proven efficacy for treating tumors. However, its use has been associated with severe side effects and eventually leads to drug resistance, thus limiting its clinical application in patients with ovarian cancer (OC). Herein, we aimed to investigate the success rate of reversing cisplatin resistance using a synthetic, multitargeted nanodrug delivery system comprising a Mn-based metal–organic framework (Mn-MOF) containing niraparib (Nira) and CDDP alongside transferrin (Tf) conjugated to the surface (Tf-Mn-MOF@Nira@CDDP; MNCT). Our results revealed that MNCT can target the tumor site, consume glutathione (GSH), which is highly expressed in drug-resistant cells, and then decompose to release the encapsulated Nira and CDDP. Nira and CDDP play a synergistic role in increasing DNA damage and apoptosis, exhibiting excellent antiproliferation, migration, and invasion activities. In addition, MNCT significantly inhibited tumor growth in tumor-bearing mice and exhibited excellent biocompatibility without side effects. Furthermore, it depleted GSH, downregulated multidrug-resistant transporter protein (MDR) expression, and upregulated tumor suppressor protein phosphatase and tensin homolog (PTEN) expression, consequently reducing DNA damage repair and reversing cisplatin resistance. These results indicate that multitargeted nanodrug delivery systems can provide a promising clinical approach to overcoming cisplatin resistance. This study provides an experimental basis for further investigation into multitargeted nanodrug delivery systems to reverse cisplatin resistance in patients with OC

Additional file 1 of Lanthanide europium MOF nanocomposite as the theranostic nanoplatform for microwave thermo-chemotherapy and fluorescence imaging

Additional file 1: Figure S1. SEM image and TEM image of EuMOF. Figure S2. The size distribution of EuMOF. Figure S3. The zeta-potential of EuMOF. Figure S4. The size distribution of EuMOF-PVP. Figure S5. The zeta-potential of EuMOF-PVP. Figure S6. The stability of EuMOF@ZIF and EuMOF at different time points in PBS (pH = 7.4), the scale bar was 1000 nm. Figure S7.The photos of EuMOF and EZ in different solution (1, PBS solution at pH 5.7, 2, PBS solution at pH 7.4) at different time after stand still. Figure S8. Infrared thermal images, temperature variation curves, temperature rise histogram of EuMOF (0, 2, 4, 8 mg/mL) under microwave irradiation for 5 min. Temperature rise histogram of EuMOF@ZIF (0, 2, 4, 8 mg/mL) under microwave irradiation for 5 min. Figure S9. (A) Infrared thermal images, (B) temperature variation curves, (C) temperature rise histogram of ZIF (0, 2, 4, 8 mg/mL) under microwave irradiation for 5 min. Figure S10. The diagram between the maximum emission peak intensity and the excitation wavelength of EuMOF. Figure S11. The diagram between the maximum emission peak intensity and the excitation wavelength of EuMOF@ZIF. Figure S12. Ultraviolet absorption curve of supernatant obtained by centrifugal washing after 1, EuMOF@ZIF loading drugs, 2, EuMOF loading drugs. Figure S13. Ultraviolet absorption curves of Apatinib at different concentrations. Figure S14. Standard curve of Apatinib at different concentrations in drug release solvent. Figure S15. Drug release rate of EZ loaded apatinib under pH = 6.5. Figure S16. Immunofluorescence images of VEGF antibody expression after co-incubation with HepG2 in different groups. Figure S17. The size distribution of EuMOF@ZIF-PEG. Figure S18. The zeta-potential of EuMOF@ZIF-PEG. Figure S19. The relative cell viability of EuMOF to HepG2 tumor cells. Figure S20. The relative cell viability of EuMOF to L929 cells. Figure S21. The relative cell viability of EuMOF to H22 tumor cells. Figure S22. Inhibition of different concentrations of EuMOF@ZIF after drug loading on H22 cells. Figure S23. Relative cell viability of H22 tumor cells under different treatments (control, EZP, MW, EZAP, EZP + MW, EZAP + MW). Figure S24. Living-dead dyeing of H22 tumor cells under different treatments (control, EZP, MW, EZAP, EZP + MW, EZAP + MW). Figure S25. Weight change of mice in acute toxicity test after injecting different doses (0, 50, 75 mg/kg) of EZAP nanocomposites. Figure S26. Blood biochemical analysis result of EZAP nanocomposites. Figure S27. Blood routine test result of EZAP nanocomposites (0, 25, 50 mg/kg). Figure S28. Representative images of different groups of tumor-bearing mice at 0 and 14 days respectively. Figure S29. Emission spectra of EuMOF@ZIF-PEG at different excitation wavelengths. Figure S30. The diagram between the maximum emission peak intensity and the excitation wavelength of EuMOF@ZIF-PEG

Encapsulating Ionic Liquid and Fe₃O₄ Nanoparticles in Gelatin Microcapsules as Microwave Susceptible Agent for MR Imaging-guided Tumor Thermotherapy

The combination of therapies and monitoring the treatment process has become a new concept in cancer therapy. Herein, gelatin-based microcapsules have been first reported to be used as microwave (MW) susceptible agent and magnetic resonance (MR) imaging contrast agent for cancer MW thermotherapy. Using the simple coacervation methods, ionic liquid (IL) and Fe₃O₄ nanoparticles (NPs) were wrapped in microcapsules, and these microcapsules showed good heating efficacy in vitro under MW irradiation. The results of cell tests indicated that gelatin/IL@Fe₃O₄ microcapsules possessed excellent compatibility in physiological environments, and they could effectively kill cancer cells with exposure to MW. The ICR mice bearing H22 tumors treated with gelatin/IL@Fe₃O₄ microcapsules were obtained an outstanding MW thermotherapy efficacy with 100% tumor elimination under ultralow density irradiation (1.8 W/cm², 450 MHz). In addition, the applicability of the microcapsules as an efficient contrast agent for MR imaging in vivo was evident. Therefore, these multifunctional microcapsules have a great potential for MR imaging-guided MW thermotherapy

Additional file 1: Figures S1–S5. of In Vivo Magnetic Resonance Imaging and Microwave Thermotherapy of Cancer Using Novel Chitosan Microcapsules

Figure S1. Size distribution of chitosan, chitosan/Fe3O4 and chitosan/Fe3O4@IL microcapsules were determined by a panel of more than 200 objects in Figure 1b. Figure S2. EDS spectrum of chitosan, chitosan/Fe3O4 and chitosan/Fe3O4@IL microcapsules. Figure S3. TG curve of chitosan, chitosan/Fe3O4 and chitosan/Fe3O4@IL microcapsules. Figure S4. Tumor weight in different groups of mice after various treatments indicated. Figure S5. Magnetization loops of chitosan/Fe3O4@IL microcapsules. Figure S6. FT-IR spectra of IL. (DOC 259 kb