<br>树突状聚赖氨酸与紫杉醇和雷公藤甲素共递送，通过 ROS 的积累增强癌症铁死亡,ACS Applied Materials & Interfaces

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树突状聚赖氨酸与紫杉醇和雷公藤甲素共递送，通过 ROS 的积累增强癌症铁死亡
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2024-04-10 , DOI: 10.1021/acsami.4c00558
Yuanyuan Wen ₁ , Kaiming Li ₂ , Mengnan Ni ₂ , Hui Jiang ₂ , Haisi Wu ₂ , Qinqi Yu ₃ , Jinyu Li ₃ , Xiaolin Li ₃ , Jifu Wei ₁ , Wei Wu ₄ , Huae Xu _{1,

2}

Affiliation

最近，据报道紫杉醇（PTX）会增加细胞内脂质活性氧（ROS）水平，引发癌细胞铁死亡。在此基础上，人们为改善PTX治疗非小细胞肺癌（NSCLC）做出了一些努力。我们前期的研究表明，雷公藤内酯醇（TPL）可以提高PTX的抗肿瘤作用。然而，溶解度差和副作用往往限制了化疗药物的应用。在本文中，我们通过聚乙二醇化第3代（G3）树突状聚赖氨酸共负载PTX和TPL构建了一种新型纳米药物递送系统（NDDS）化学合成（PTX-TPL-PEG-PLL，PTPP），该系统具有肿瘤靶向能力和良好的溶解度。此外，我们证明TPL可以通过调节NF-κB信号通路诱导ROS产生，从而增强PTX的铁死亡诱导作用。此外，PTPP诱导的铁死亡可以通过抑制P-gp、GPX4和SLC7A11的水平来改善化疗耐药性。此外，我们确定铁死亡可能通过增加 CD8 ⁺ T 细胞和 IFN-γ ⁺细胞的表达同时减少 Treg 细胞来增强免疫反应。总的来说，PTPP可能是NSCLC治疗的潜在系统。

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Dendritic Polylysine with Paclitaxel and Triptolide Codelivery for Enhanced Cancer Ferroptosis through the Accumulation of ROS

Recently, paclitaxel (PTX) was reported to increase intracellular lipid reactive oxygen species (ROS) levels, triggering cancer cell ferroptosis. Based on this, some efforts had been made to improve PTX treatment for non-small-cell lung cancer (NSCLC). Our previous studies demonstrated that triptolide (TPL) could improve the antitumor effect of PTX. Nevertheless, the poor solubility and side effects often limit the application of chemotherapy drugs. In this paper, we constructed a novel nanodrug delivery system (NDDS) chemosynthesis by PEGylated generation 3 (G3) dendritic polylysine coloaded with PTX and TPL (PTX-TPL-PEG-PLL, PTPP), which was endowed with the ability of tumor targeting and favorable solubility. In addition, we demonstrated that TPL could induce ROS generation by regulating the NF-κB signaling pathway to enhance the ferroptosis-induced effect of PTX. Besides, ferroptosis induced by PTPP could improve chemoresistance through inhibiting the level of P-gp, GPX4, and SLC7A11. Furthermore, we determined that ferroptosis may strengthen the immune response by increasing the expression of CD8⁺ T cells and IFN-γ⁺ cells while decreasing Treg cells. In general, PTPP may be a potential system for NSCLC treatment.

更新日期：2024-04-10

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