Cabazitaxel-loaded human serum albumin nanoparticles combined with TGFβ-1 siRNA lipid nanoparticles for the treatment of paclitaxel-resistant non-small cell lung cancer

作者：Tan, Tiantian; Feng, Yuxin; Wang, Weimin; Wang, Rongrong; Yin, Liyan; Zeng, Yiying; Zeng, Zhaowu^*; Xie, Tian^*

来源：Cancer Nanotechnology, 2023, 14(1): 70.

DOI：10.1186/s12645-023-00194-7

• Cabazitaxel
• Albumin
• Paclitaxel-resistant NSCLC
• Lipid nanoparticles
• TGF beta-1 siRNA

Background: In the current treatment of non-small cell lung cancer (NSCLC), traditional chemotherapy causes high toxicity, so it is necessary to develop safe chemical drug delivery vehicles clinically. Chemotherapy monotherapy is prone to drug resistance. Chemotherapy combined with other therapies such as nucleic acid drugs is an effective way to avoid drug resistance and the toxicity of continuous chemotherapy. In this study, chemotherapy and siRNA therapy were combined to treat paclitaxel-resistant NSCLC in order to increase efficacy and reduce toxicity. This study aims to develop a cabazitaxel-loaded human serum albumin nanoparticles (CTX-HSA-NPs) to improve the toxicity of traditional CTX-Tween 80 and increase targeting, and to develop a TGF beta-1 siRNA lipid Nanoparticles (TGF beta-1 siRNA LNP) combined with chemotherapy in the treatment of paclitaxel-resistant NSCLC. @@@ Results: This study prepared CTX-HSA-NPs and TGF beta-1 siRNA LNP had small particle size, high encapsulation efficiency (EE). CTX-HSA-NPs lyophilized powder has high stability after dissolved. The antitumor effect of CTX-HSA-NPs on paclitaxel-resistant NSCLC was higher than that of CTX-Tween, and the toxicity was 1.8 times lower than that of CTX-Tween. More importantly, the combined treatment of TGF beta-1 siRNA LNP and CTX-HSA-NPs could effectively improve the antitumor efficacy of paclitaxel-resistant NSCLC in vivo and in vitro. The results of tumor immunohistochemistry showed that TGF beta-1 siRNA LNP significantly inhibited the expression of TGF beta-1, and compared with other groups, the expression of P-gp after low-dose CTX-HSA-NPs treatment was lower, which did not cause obvious drug resistance. @@@ Conclusions: The antitumor effect of CTX-HSA-NPs on paclitaxel-resistant NSCLC was higher than that of CTX-Tween, and the toxicity was lower than that of CTX-Tween. TGF beta-1 siRNA LNP can treat paclitaxel-resistant NSCLC by inhibiting the express of TGF beta-1 mRNA. The combined treatment of TGF beta-1 siRNA LNP and CTX-HSA-NPs could effectively improve the antitumor efficacy of paclitaxel-resistant NSCLC. A combination therapy of chemotherapy and nucleic acid drugs could be an effective approach for treating paclitaxel-resistant NSCLC.

• 单位
  广东药学院; 杭州师范大学