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已发表论文
体外评估针对 4T1 乳腺癌细胞的线粒体靶向穿心莲内酯纳米颗粒的作用
Authors Yuan X, Bi Y, Liu J, Xu W, Li M, Li K, Zou Y, Wang X, Chen Y, Yang Q
Received 28 February 2025
Accepted for publication 5 December 2025
Published 20 December 2025 Volume 2025:20 Pages 15395—15414
DOI https://doi.org/10.2147/IJN.S525568
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Dong Wang
Xiaoyan Yuan,1,* Yunfeng Bi,2,* Ji Liu,1 Wenhao Xu,1 Mingjuan Li,3 Kexin Li,1 Yan Zou,1 Xing Wang,4 Yanqing Chen,1 Qiming Yang1
1Department of Pharmacy, Panzhihua Central Hospital, Panzhihua, People’s Republic of China; 2Department of Pharmacy, Pingbian Maternal and Child Health Hospital, Honghe, People’s Republic of China; 3Department of Pharmacy, Chuantou Xichang Hospital, Xichang, People’s Republic of China; 4College of Medicine, Southwest Jiaotong University, Chengdu, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xiaoyan Yuan, Email yuanliuswf@sina.com Qiming Yang, Email 479686812@qq.com
Objective: Andrographolide (AG) demonstrated promising anticancer efficacy against the initiation and progression of breast cancer by triggering the mitochondria-mediated intrinsic apoptotic pathway. However, its clinical translation is still hindered by drawbacks such as poor bioavailability and off-target effects; therefore, an optimized drug-delivery system that minimizes these effects is urgently needed. To address these issues, we successfully developed a mitochondria-targeting nanocarrier (TPP-PEG-PCL) with high drug-loading capacity and excellent biocompatibility.
Methods: The mitochondria-targeting copolymer (TPP-PEG-PCL) was synthesized chemically and used to prepare AG-loaded polymeric micelles (TPP-PEG-PCL@AG) by solvent-evaporation method. In vitro, the blank micelles were first evaluated for biocompatibility with mouse breast-cancer cells (4T1) and endothelial cells (EC). Subsequently, a panel of cellular assays was performed on 4T1 cells to compare the antitumor activity of free AG, PEG-PCL@AG, and TPP-PEG-PCL@AG, confirming the enhanced cancer-cell killing achieved through mitochondria-targeted delivery of AG.
Results: The results showed that TPP-PEG-PCL micelles were readily taken up by 4T1 cells and selectively accumulated in mitochondria with a Pearson’s correlation (Rr) 0.47 compared to 0.25 in PEG-PCL micelles group, leading to a pronounced inhibition of proliferation and migration. By elevating intracellular ROS, decreasing mitochondrial membrane potential, and activating the caspase cascade, the micelles induced apoptosis and thereby achieved mitochondria-targeted potentiation of TPP-PEG-PCL@AG. However, this study is limited to in vitro validation using the 4T1 murine model, and further in vivo investigations are warranted to assess translational efficacy and potential systemic toxicity..
Conclusion: PCL-PEG nanoparticles decorated with TPP combine pronounced mitochondria-targeting specificity, high drug-loading capacity, excellent biocompatibility and readily tunable architecture, making them an ideal platform for constructing a precise mitochondrial-intervention system for AG. This strategy is particularly attractive for tumor-targeted delivery of AG and opens a new avenue for its clinical translation.
Keywords: andrographolide, nanoparticles, mitochondrial targeting, anti-breast cancer
1Department of Pharmacy, Panzhihua Central Hospital, Panzhihua, People’s Republic of China; 2Department of Pharmacy, Pingbian Maternal and Child Health Hospital, Honghe, People’s Republic of China; 3Department of Pharmacy, Chuantou Xichang Hospital, Xichang, People’s Republic of China; 4College of Medicine, Southwest Jiaotong University, Chengdu, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xiaoyan Yuan, Email yuanliuswf@sina.com Qiming Yang, Email 479686812@qq.com
Objective: Andrographolide (AG) demonstrated promising anticancer efficacy against the initiation and progression of breast cancer by triggering the mitochondria-mediated intrinsic apoptotic pathway. However, its clinical translation is still hindered by drawbacks such as poor bioavailability and off-target effects; therefore, an optimized drug-delivery system that minimizes these effects is urgently needed. To address these issues, we successfully developed a mitochondria-targeting nanocarrier (TPP-PEG-PCL) with high drug-loading capacity and excellent biocompatibility.
Methods: The mitochondria-targeting copolymer (TPP-PEG-PCL) was synthesized chemically and used to prepare AG-loaded polymeric micelles (TPP-PEG-PCL@AG) by solvent-evaporation method. In vitro, the blank micelles were first evaluated for biocompatibility with mouse breast-cancer cells (4T1) and endothelial cells (EC). Subsequently, a panel of cellular assays was performed on 4T1 cells to compare the antitumor activity of free AG, PEG-PCL@AG, and TPP-PEG-PCL@AG, confirming the enhanced cancer-cell killing achieved through mitochondria-targeted delivery of AG.
Results: The results showed that TPP-PEG-PCL micelles were readily taken up by 4T1 cells and selectively accumulated in mitochondria with a Pearson’s correlation (Rr) 0.47 compared to 0.25 in PEG-PCL micelles group, leading to a pronounced inhibition of proliferation and migration. By elevating intracellular ROS, decreasing mitochondrial membrane potential, and activating the caspase cascade, the micelles induced apoptosis and thereby achieved mitochondria-targeted potentiation of TPP-PEG-PCL@AG. However, this study is limited to in vitro validation using the 4T1 murine model, and further in vivo investigations are warranted to assess translational efficacy and potential systemic toxicity..
Conclusion: PCL-PEG nanoparticles decorated with TPP combine pronounced mitochondria-targeting specificity, high drug-loading capacity, excellent biocompatibility and readily tunable architecture, making them an ideal platform for constructing a precise mitochondrial-intervention system for AG. This strategy is particularly attractive for tumor-targeted delivery of AG and opens a new avenue for its clinical translation.
Keywords: andrographolide, nanoparticles, mitochondrial targeting, anti-breast cancer