Dual-drug controllable co-assembly nanosystem for targeted and synergistic treatment of hepatocellular carcinoma.
Dual-drug controllable co-assembly nanosystem for targeted and synergistic treatment of hepatocellular carcinoma.
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DOI：
10.1016/j.jcis.2023.11.109
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发表时间：
2023-11
影响因子：
9.9
通讯作者：
Jing Le;Xun-Huan Song;Ling Tong;Ying-Qi Lin;Ke-Ke Feng-Ke;Yi-Fan Tu;Yong-Shan Hu;Jing-Wei Shao-Jing-Wei-Sh
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文献类型：
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作者：
Jing Le;Xun-Huan Song;Ling Tong;Ying-Qi Lin;Ke-Ke Feng-Ke;Yi-Fan Tu;Yong-Shan Hu;Jing-Wei Shao-Jing-Wei-Sh
由于肝癌的异质性、多药耐药和靶点聚集性差，化疗药物对肝癌的疗效不理想。因此，具有精确药物递送的多模式治疗变得越来越受欢迎。本文通过一锅法将细胞穿透肽和适体包被到索拉非尼（索拉）、熊果酸（UA）和吲哚菁绿色（ICG）缩合纳米药物（USI NPs）的表面，成功构建了细胞穿透肽-适体双重修饰纳米复合物（USILA NPs），用于靶向和协同治疗HCC。USILA纳米粒在HepG 2和H22细胞中显示出更高的细胞摄取和细胞毒性，具有高表达的上皮细胞粘附分子（EpCAM）。此外，这些纳米颗粒引起更显着的线粒体膜电位降低和细胞凋亡。这些纳米颗粒可以选择性地积累在H22荷瘤小鼠的肿瘤部位，并在ICG荧光的帮助下检测到;此外，它们比单一疗法更好地延缓肿瘤生长。因此，USILA纳米粒可以实现双重药物的靶向输送和诊断与治疗的一体化。此外，在共同施用iRGD肽（一种具有更好渗透促进能力的肿瘤穿透肽）或程序性细胞死亡配体1（PD-L1）抗体以逆转肿瘤微环境中的免疫抑制状态后，效果更显著。USILA NPs + iRGD肽或USILA NPs + PD-L1抗体的肿瘤抑制率分别为72.38%和67.91%，具有良好的治疗安全性。总的来说，这种复合纳米系统可以作为一种有前途的靶向工具，并为增强HCC协同治疗提供有效的干预策略。
The effectiveness of chemotherapeutic agents for hepatocellular carcinoma (HCC) is unsatisfactory because of tumor heterogeneity, multidrug resistance, and poor target accumulation. Therefore, multimodality-treatment with accurate drug delivery has become increasingly popular. Herein, a cell penetrating peptide-aptamer dual modified-nanocomposite (USILA NPs) was successfully constructed by coating a cell penetrating peptide and aptamer onto the surface of sorafenib (Sora), ursolic acid (UA) and indocyanine green (ICG) condensed nanodrug (USI NPs) via one-pot assembly for targeted and synergistic HCC treatment. USILA NPs showed higher cellular uptake and cytotoxicity in HepG2 and H22 cells, with a high expression of epithelial cell adhesion molecule (EpCAM). Furthermore, these NPs caused more significant mitochondrial membrane potential reduction and cell apoptosis. These NPs could selectively accumulate at the tumor site of H22 tumor-bearing mice and were detected with the help of ICG fluorescence; moreover, they retarded tumor growth better than monotherapy. Thus, USILA NPs can realize the targeted delivery of dual drugs and the integration of diagnosis and treatment. Moreover, the effects were more significant after co-administration of iRGD peptide, a tumor-penetrating peptide with better penetration promoting ability or programmed cell death ligand 1 (PD-L1) antibody for the reversal of the immunosuppressive state in the tumor microenvironment. The tumor inhibition rates of USILA NPs + iRGD peptide or USILA NPs + PD-L1 antibody with good therapeutic safety were 72.38 % and 67.91 % compared with control, respectively. Overall, this composite nanosystem could act as a promising targeted tool and provide an effective intervention strategy for enhanced HCC synergistic treatment.