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<p>TXA9, a cardiac glycoside isolated from the root of <i>Streptocaulon juventas</i> (Lour.) Merr., with better therapeutic effect in vitro on non-small cell lung cancer (NSCLC) than cisplatin and has no toxic side effects on the body. However, poor water solubility and rapid metabolism limited its clinical application. Multi-arm star PEG have many advantages over linear PEG, such as high drug loading due to more terminals and better anti-hemodilution ability, which have become popular carriers for drug delivery. In this study, to improve the efficacy of TXA9, 6/8armPEG<sub>n</sub>-Glycine Carbamate (Gly) (<i>n</i> = 10, 20, and 40&#xa0;kDa) were used as carriers to prepare star PEG-TXA9 conjugates. The particle size and zeta potential of six prodrug NPs for effective tumor targeting, with suitable drug loading, and good water solubility. Compared with free TXA9, 6/8APG<sub>n</sub>-T NPs had more significant anti-tumor effects in vitro. Since the multi-arm star PEG formed an “umbrella” structure on the surface of NPs, the 8APG<sub>40k</sub>-T NPs with the best pharmacokinetic properties increased half-life of TXA9 about 60 times in vivo. In addition, the arm numbers and molecular weight of multi-arm star PEGs significantly influenced the in vivo destiny of prodrugs. In vivo experiments showed that the same dose of 8APG<sub>40k</sub>-T NPs increased the tumor inhibition rate about 3.56 or 1.22 times compared with TXA9 or cisplatin, and had good biocompatibility. This study provides a simple but effective strategy to solve the challenges caused by the poor water solubility and short half-life of TXA9 for developing the TXA9 as a safe and effective drug against NSCLC.</p> Graphical Abstract <p></p>

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Self-assembly of multi-arm star PEG containing TXA9 into nanoparticle for the efficient chemotherapy of NSCLC

  • 期刊论文

  • 发表日期：

    2025年1月20日

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  • Qilong Wang,
  • Zhe Liu,
  • Jiale Yao,
  • Haosheng Xie,
  • Zhihui Liu,
  • Jianxiu Zhai,
  • Sikai Li,
  • Jia Ming Zhang,
  • Na Han,
  • Jun Yin

摘要

TXA9, a cardiac glycoside isolated from the root of Streptocaulon juventas (Lour.) Merr., with better therapeutic effect in vitro on non-small cell lung cancer (NSCLC) than cisplatin and has no toxic side effects on the body. However, poor water solubility and rapid metabolism limited its clinical application. Multi-arm star PEG have many advantages over linear PEG, such as high drug loading due to more terminals and better anti-hemodilution ability, which have become popular carriers for drug delivery. In this study, to improve the efficacy of TXA9, 6/8armPEGn-Glycine Carbamate (Gly) (n = 10, 20, and 40 kDa) were used as carriers to prepare star PEG-TXA9 conjugates. The particle size and zeta potential of six prodrug NPs for effective tumor targeting, with suitable drug loading, and good water solubility. Compared with free TXA9, 6/8APGn-T NPs had more significant anti-tumor effects in vitro. Since the multi-arm star PEG formed an “umbrella” structure on the surface of NPs, the 8APG40k-T NPs with the best pharmacokinetic properties increased half-life of TXA9 about 60 times in vivo. In addition, the arm numbers and molecular weight of multi-arm star PEGs significantly influenced the in vivo destiny of prodrugs. In vivo experiments showed that the same dose of 8APG40k-T NPs increased the tumor inhibition rate about 3.56 or 1.22 times compared with TXA9 or cisplatin, and had good biocompatibility. This study provides a simple but effective strategy to solve the challenges caused by the poor water solubility and short half-life of TXA9 for developing the TXA9 as a safe and effective drug against NSCLC.

Graphical Abstract