Scholarlink

Background <p>Glioblastoma (GBM) is highly resistant to conventional chemoradiotherapy. Platinum nanoparticles (Pt-NPs) have potential applications as both physical and biological radiosensitizers. Temozolomide (TMZ), the standard chemotherapeutic agent for GBM, induces cancer cell death via DNA alkylation. In this study, the potential enhancement of the efficacy of clinically relevant megavoltage X-ray irradiation in U87 glioblastoma cells was investigated by combining Pt-NPs and TMZ.</p> Methods <p>Initially, Pt-NPs were synthesized and characterized using SEM, EDX, and DLS analysis. The cellular uptake of Pt-NPs was evaluated using confocal laser scanning microscopy (CLSM) and quantified by flow cytometry. Subsequently, to assess their radiosensitizing properties, U87 cells were exposed to Pt-NPs (IC10), TMZ (IC20), or 2&#xa0;Gy of X-ray irradiation, either individually or in combination. A comprehensive series of assays, including cytotoxicity tests, clonogenic survival analysis, γ-H2AX immunofluorescence for DNA double-strand breaks, and evaluations of apoptosis and cell cycle distribution, was conducted.</p> Results <p>The synthesized Pt-NPs exhibited an average diameter of 121 ± 13&#xa0;nm and a zeta potential of -42 ± 1.4&#xa0;mV. CLSM and flow cytometry confirmed efficient intracellular uptake of Pt-NPs by U87 glioblastoma cells, with approximately 46% of cells showing internalization. In terms of radiosensitization, the triple combination (Pt-NPs, TMZ, and X-ray irradiation) almost eliminated clonogenic survival, resulting in significantly greater cytotoxicity than single or dual treatments. γ-H2AX staining revealed extensive DNA damage in the triple group compared with the control and dual combination groups. The levels of apoptosis were highest after triple combination, and cell cycle analysis revealed significant S-phase arrest, accompanied by disruption of the G2/M checkpoint. Additionally, Pt-NPs alone caused moderate DNA damage and apoptosis but significantly enhanced the effects of TMZ and irradiation when used in combination.</p> Conclusion <p>Pt-NPs enhance the cytotoxic effects of TMZ and radiation by increasing DNA damage and disrupting cell cycle regulation. These findings emphasize the triple combination as a promising synergistic nanotherapeutic approach to overcome treatment resistance.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Platinum nanoparticles combined with temozolomide enhance radiosensitivity of U87 glioblastoma cells under megavoltage X-Ray irradiation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月8日

查看全文
  • Peerawit Soonthornchookiat,
  • Chanyatip Suwannasing,
  • Nittiya Suwannasom,
  • Hans Bäumler,
  • Chatrawut Pattaweerakul,
  • Worawat Songjang,
  • Sarawut Kumphune,
  • Ausanai Prapan

摘要

Background

Glioblastoma (GBM) is highly resistant to conventional chemoradiotherapy. Platinum nanoparticles (Pt-NPs) have potential applications as both physical and biological radiosensitizers. Temozolomide (TMZ), the standard chemotherapeutic agent for GBM, induces cancer cell death via DNA alkylation. In this study, the potential enhancement of the efficacy of clinically relevant megavoltage X-ray irradiation in U87 glioblastoma cells was investigated by combining Pt-NPs and TMZ.

Methods

Initially, Pt-NPs were synthesized and characterized using SEM, EDX, and DLS analysis. The cellular uptake of Pt-NPs was evaluated using confocal laser scanning microscopy (CLSM) and quantified by flow cytometry. Subsequently, to assess their radiosensitizing properties, U87 cells were exposed to Pt-NPs (IC10), TMZ (IC20), or 2 Gy of X-ray irradiation, either individually or in combination. A comprehensive series of assays, including cytotoxicity tests, clonogenic survival analysis, γ-H2AX immunofluorescence for DNA double-strand breaks, and evaluations of apoptosis and cell cycle distribution, was conducted.

Results

The synthesized Pt-NPs exhibited an average diameter of 121 ± 13 nm and a zeta potential of -42 ± 1.4 mV. CLSM and flow cytometry confirmed efficient intracellular uptake of Pt-NPs by U87 glioblastoma cells, with approximately 46% of cells showing internalization. In terms of radiosensitization, the triple combination (Pt-NPs, TMZ, and X-ray irradiation) almost eliminated clonogenic survival, resulting in significantly greater cytotoxicity than single or dual treatments. γ-H2AX staining revealed extensive DNA damage in the triple group compared with the control and dual combination groups. The levels of apoptosis were highest after triple combination, and cell cycle analysis revealed significant S-phase arrest, accompanied by disruption of the G2/M checkpoint. Additionally, Pt-NPs alone caused moderate DNA damage and apoptosis but significantly enhanced the effects of TMZ and irradiation when used in combination.

Conclusion

Pt-NPs enhance the cytotoxic effects of TMZ and radiation by increasing DNA damage and disrupting cell cycle regulation. These findings emphasize the triple combination as a promising synergistic nanotherapeutic approach to overcome treatment resistance.