<p>The simultaneous use of multiple therapeutic methods as combinational therapy could be a promising strategy to overcome glioblastoma resistance. We introduced a hybrid Bismuth-Niosomes nanocarriers containing Pi3K inhibitor and doxorubicin drug and targeted by glutathione and glutamate ligands (BiNPs-NISM-Dox/Pi3Ki@BSA-GSH-Glu). Finally, its anticancer effects were evaluated the in vitro on U87 glioblastoma cell line. The nanosystems were synthesized using a modified thin-film hydration technique and characterized using FTIR, UV-vis, DLS, TEM, FESEM, EDX, in vitro release, and hemolysis tests. The anticancer efficacy of nanosystems was evaluated through cellular uptake, cell viability, gene expression, cell-cycle, apoptosis, and scratch assays under both treatment conditions (without/with 2&#xa0;Gy X-irradiation). Characterization results such as proper interaction among agent groups, nanometer size, negative charge, spherical morphology, good stability in biological medium, time/pH-dependent drug release, hemocompatibility, and high cellular internalization confirmed the correct synthesis of nanosystems. The treatment of U87 cells with BiNPs-NISM-Dox-Pi3Ki@BSA-GSH-Glu nanosystem under both conditions of X-ray exposure led to cell viability reduction, <i>Vimentin</i>, <i>Cyclin D1</i>, and <i>Bcl-xL</i> genes downregulation, cell cycle arrest (sub-G1 phase), apoptosis induction, and cell migration inhibition. The synergistic effects of final formulation of nanosystem along with X-irradiation exposure is statistically significant compared to No X-irradiation condition. The obtained results revealed that BiNPs-NISM-Dox-Pi3Ki@BSA-GSH-Glu nanosystem could be considered as a novel promising combinational therapy approach to overcome conventional limitations of current glioma cancer treatments through targeted drug delivery, signaling pathway inhibition, chemoradiotherapy. Further investigations including in vivo and clinical studies for assess reducing the side effects of drugs and optimum efficacy is required.</p>

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Dual-targeted glutathione-glutamate functionalized Bismuth-Niosomes hybrid nanosystem for co-delivery of doxorubicin and Pi3K inhibitor into U87 glioblastoma cells

  • Zahra Bigdelou,
  • Mahmoud Gharbavi,
  • Ghasem Bagherpour,
  • Hamed Rezaeejam,
  • Behrooz Johari

摘要

The simultaneous use of multiple therapeutic methods as combinational therapy could be a promising strategy to overcome glioblastoma resistance. We introduced a hybrid Bismuth-Niosomes nanocarriers containing Pi3K inhibitor and doxorubicin drug and targeted by glutathione and glutamate ligands (BiNPs-NISM-Dox/Pi3Ki@BSA-GSH-Glu). Finally, its anticancer effects were evaluated the in vitro on U87 glioblastoma cell line. The nanosystems were synthesized using a modified thin-film hydration technique and characterized using FTIR, UV-vis, DLS, TEM, FESEM, EDX, in vitro release, and hemolysis tests. The anticancer efficacy of nanosystems was evaluated through cellular uptake, cell viability, gene expression, cell-cycle, apoptosis, and scratch assays under both treatment conditions (without/with 2 Gy X-irradiation). Characterization results such as proper interaction among agent groups, nanometer size, negative charge, spherical morphology, good stability in biological medium, time/pH-dependent drug release, hemocompatibility, and high cellular internalization confirmed the correct synthesis of nanosystems. The treatment of U87 cells with BiNPs-NISM-Dox-Pi3Ki@BSA-GSH-Glu nanosystem under both conditions of X-ray exposure led to cell viability reduction, Vimentin, Cyclin D1, and Bcl-xL genes downregulation, cell cycle arrest (sub-G1 phase), apoptosis induction, and cell migration inhibition. The synergistic effects of final formulation of nanosystem along with X-irradiation exposure is statistically significant compared to No X-irradiation condition. The obtained results revealed that BiNPs-NISM-Dox-Pi3Ki@BSA-GSH-Glu nanosystem could be considered as a novel promising combinational therapy approach to overcome conventional limitations of current glioma cancer treatments through targeted drug delivery, signaling pathway inhibition, chemoradiotherapy. Further investigations including in vivo and clinical studies for assess reducing the side effects of drugs and optimum efficacy is required.