Citation: Lin Li, Bingjun Sun, Jin Sun, Lin Chen, Zhonggui He. Binary prodrug nanoassemblies combining chemotherapy and ferroptosis activation for efficient triple-negative breast cancer therapy[J]. Chinese Chemical Letters, ;2024, 35(10): 109538. doi: 10.1016/j.cclet.2024.109538 shu

Binary prodrug nanoassemblies combining chemotherapy and ferroptosis activation for efficient triple-negative breast cancer therapy

Lin Li ^a ,
Bingjun Sun ^b ,
Jin Sun ^b ,
Lin Chen ^{a, *,} ,
Zhonggui He ^{b, *,}

a.
Department of Pharmacy, Women and Children’s Hospital of Chongqing Medical University/Chongqing Health Center for Women and Children, Chongqing 401147, China
b.
Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China

clfxmm@163.com

hezhgui_student@aliyun.com

Received Date: 6 November 2023
Revised Date: 7 January 2024
Accepted Date: 12 January 2024
Available Online: 20 January 2024

Figures(5)

Chemotherapy has been recommended as the standard protocol for triple-negative breast cancer (TNBC) at the advanced stage. However, the current treatment is unsatisfactory due to inefficient drug accumulation and rapid chemo-resistance. Thus, rational design of advanced drug delivery systems that can induce multiple cell death pathways is a promising strategy to combat TNBC. Ferroptosis is a powerful non-apoptotic cell death modality, showing potential in tumor inhibition. Herein, we propose a binary prodrug nanoassemblies that combines chemotherapy with ferroptosis for TNBC treatment. In this system, paclitaxel is linked with paracetamol (ferroptosis activator) by a disulfide linkage to construct self-assembly prodrug. Meanwhile, 2-distearoyl-sn-glycerol-3-phosphoethanolamine-N-methyl(polyethylene glycol)-2000-tyrosine (DSPE-PEG_2k-tyrosine) is applied for large neutral amino acid transporter 1 (LAT1) targeting, which is highly expressed in TNBC. The prodrug nanoassemblies exhibit good stability and a glutathione (GSH)-responsive release profile. Furthermore, the LAT1-targeted nanoassemblies show stronger cytotoxicity, higher cellular uptake, and more obvious ferroptosis activation than non-decorated ones. In a TNBC mice model, the prodrug nanoassemblies demonstrate strong anti-tumor efficacy. The application of ferroptosis-assisting chemotherapy may provide a promising strategy for TNBC therapy.
- Prodrug nanoassemblies,
- Paclitaxel,
- Ferroptosis,
- LAT1,
- Triple-negative breast cancer
1. [1]
  B.D. Lehmann, J.A. Bauer, X. Chen, et al., J. Clin. Invest. 121 (2011) 2750–2767. doi: 10.1172/JCI45014
2. [2]
  K.A. Won, C. Spruck, Int. J. Oncol. 57 (2020) 1245–1261. doi: 10.3892/ijo.2020.5135
3. [3]
  S. Wang, H. Liao, F. Li, D. Ling, Chin. Chem. Lett. 30 (2019) 847–852. doi: 10.1016/j.cclet.2019.03.025
4. [4]
  X. Jiang, B.R. Stockwell, M. Conrad, Nat. Rev. Mol. Cell Biol. 22 (2021) 266–282. doi: 10.1038/s41580-020-00324-8
5. [5]
  T. Xu, W. Ding, X. Ji, et al., J. Cell. Mol. Med. 23 (2019) 4900–4912. doi: 10.1111/jcmm.14511
6. [6]
  J. Zheng, M. Conrad, Cell Metab. 32 (2020) 920–937. doi: 10.1016/j.cmet.2020.10.011
7. [7]
  F. Yang, Y. Xiao, J.H. Ding, et al., Cell Metab. 35 (2023) 84–100. doi: 10.1117/12.2668164
8. [8]
  B. Niu, K. Liao, Y. Zhou, et al., Biomaterials 277 (2021) 121110. doi: 10.1016/j.biomaterials.2021.121110
9. [9]
  J. Li, Y. Zhou, J. Liu, et al., J. Control. Release 352 (2022) 313–327. doi: 10.1016/j.jconrel.2022.10.025
10. [10]
  Z. Zhou, H. Liang, R. Yang, et al., Angew. Chem. Int. Ed. 61 (2022) e202202843. doi: 10.1002/anie.202202843
11. [11]
  M. Yu, C. Gai, Z. Li, et al., Cancer Sci. 110 (2019) 3173–3182. doi: 10.1111/cas.14181
12. [12]
  D. Qi, L. Xing, L. Shen, et al., Chin. Chem. Lett. 33 (2022) 4595–4599. doi: 10.1016/j.cclet.2022.03.105
13. [13]
  R. Ma, L. Fang, L. Chen, et al., Theranostics 12 (2022) 2266–2289. doi: 10.7150/thno.66663
14. [14]
  Y. Xie, W. Hou, X. Song, et al., Cell Death Diff. 23 (2016) 369–379. doi: 10.1038/cdd.2015.158
15. [15]
  Y. Su, B. Zhao, L. Zhou, et al., Cancer Lett. 483 (2020) 127–136. doi: 10.1016/j.canlet.2020.02.015
16. [16]
  B. Sun, C. Luo, X. Zhang, et al., Nat. Commun. 10 (2019) 3211. doi: 10.1038/s41467-019-11193-x
17. [17]
  Y. Yang, B. Sun, S. Zuo, et al., Sci. Adv. 6 (2020) eabc1725. doi: 10.1126/sciadv.abc1725
18. [18]
  Y. Li, L. Li, Q. Jin, et al., Asian J. Pharm. Sci. 17 (2022) 241–252. doi: 10.1002/ab.22002
19. [19]
  T. Liu, L. Li, S. Wang, et al., Nat. Commun. 13 (2022) 7228. doi: 10.1038/s41467-022-35033-7
20. [20]
  Y. Zhou, Y. Zhang, C. Jiang, et al., Small 19 (2023) 2300594. doi: 10.1002/smll.202300594
21. [21]
  L. Li, X. Di, M. Wu, et al., Nanomedicine 13 (2017) 987–998. doi: 10.1016/j.nano.2016.11.012
22. [22]
  Z. Zhao, X. Liu, M. Hou, et al., Adv. Mater. 34 (2022) 2110560. doi: 10.1002/adma.202110560
23. [23]
  L. Song, X. Chen, L. Mi, et al., Cancer Sci. 111 (2020) 4242–4256. doi: 10.1111/cas.14648
24. [24]
  J.J. Arroyo-Crespo, A. Armiñán, D. Charbonnier, et al., Int. J. Cancer 145 (2019) 2267–2281. doi: 10.1002/ijc.32270
1. [1]
  Chao Liu , Liming Gong , Yanhong Liu , Shuangqing Wang , Hao Wu , Liqing Chen , Mingji Jin , Zhonggao Gao , Wei Huang . Lipoic acid-locked reduction-responsive core-cross-linked micelles delivering paclitaxel for triple-negative breast cancer treatment. Chinese Chemical Letters, 2025, 36(8): 110570-. doi: 10.1016/j.cclet.2024.110570
2. [2]
  Wenfeng Zang , Yixin Sun , Jingyi Zhang , Yanzhong Hao , Qianhui Jin , Hongying Xiao , Zuo Zhang , Xianbao Shi , Jin Sun , Zhonggui He , Cong Luo , Bingjun Sun . Two-tailed modification module tuned steric-hindrance effect enabling high therapeutic efficacy of paclitaxel prodrug nanoassemblies. Chinese Chemical Letters, 2025, 36(5): 110230-. doi: 10.1016/j.cclet.2024.110230
3. [3]
  Yuequan Wang , Congtian Wu , Chengcheng Feng , Qin Chen , Zhonggui He , Shenwu Zhang , Cong Luo , Jin Sun . Spatiotemporally-controlled supramolecular hybrid nanoassembly enabling ferroptosis-augmented photodynamic immunotherapy of cancer. Chinese Chemical Letters, 2025, 36(3): 109902-. doi: 10.1016/j.cclet.2024.109902
4. [4]
  Guanghui Lin , Jieyao Chen , Xiaojia Liu , Yitong Lin , Xudong Zhu , Guotao Yuan , Bowen Yang , Shuanshuan Guo , Yue Pan , Jianhua Zhou . Sustained modulation of tumor microenvironment via sorafenib-loaded mesoporous ferromanganese nanozymes for enhanced apoptosis-ferroptosis cancer therapy. Chinese Chemical Letters, 2025, 36(8): 111018-. doi: 10.1016/j.cclet.2025.111018
5. [5]
  Yanjun Cai , Yong Jiang , Yu Chen , Erzhuo Cheng , Yuan Gu , Yuwei Li , Qianqian Liu , Jian Zhang , Jifang Liu , Shisong Han , Bin Yang . Amplifying STING activation and immunogenic cell death by metal-polyphenol coordinated nanomedicines for enhanced cancer immunotherapy. Chinese Chemical Letters, 2025, 36(5): 110437-. doi: 10.1016/j.cclet.2024.110437
6. [6]
  Zhendong Liu , Sainan Liu , Bin Liu , Qi Meng , Meng Yuan , Chunzheng Yang , Yulong Bian , Ping'an Ma , Jun Lin . Fe(Ⅲ)-juglone nanoscale coordination polymers for cascade chemodynamic therapy through synergistic ferroptosis and apoptosis strategy. Chinese Chemical Letters, 2024, 35(11): 109626-. doi: 10.1016/j.cclet.2024.109626
7. [7]
  Yan Gao , Zi-Lin Song , Shuang Yu , Xiu-Li Zhao , Da-Wei Chen , Ming-Xi Qiao . Enhanced ferroptosis by a nanoparticle mimicking hemoglobin coordinate pattern with self-supplying hydrogen peroxide. Chinese Chemical Letters, 2025, 36(5): 110097-. doi: 10.1016/j.cclet.2024.110097
8. [8]
  Quan Lu , Lulu Zhang , Zihan Chen , Jiajia Lv , Jie Gao , Xinmin Li , Hongyu Li , Wen Shi , Xiaohua Li , Huimin Ma , Zeli Yuan . A lipid droplet-targeting fluorescence probe for monitoring of lipid peroxidation in ferroptosis and non-alcoholic fatty liver disease. Chinese Chemical Letters, 2025, 36(8): 110620-. doi: 10.1016/j.cclet.2024.110620
9. [9]
  Zheng-Biao Zou , Tai-Zong Wu , Chun-Lan Xie , Yuan Wang , Yan Li , Gang Zhang , Rong Chao , Lian-Zhong Luo , Li-Sheng Li , Xian-Wen Yang . neo-Dicitrinols A–C: Unprecedented PKS-NRPS hybrid citrinin dimers with ferroptosis inhibitory activity from the deep-sea-derived Penicillium citrinum W22. Chinese Chemical Letters, 2024, 35(12): 109723-. doi: 10.1016/j.cclet.2024.109723
10. [10]
  Yi Cao , Xiaojiao Ge , Yuanyuan Wei , Lulu He , Aiguo Wu , Juan Li . Tumor microenvironment-activatable neuropeptide-drug conjugates enhanced tumor penetration and inhibition via multiple delivery pathways and calcium deposition. Chinese Chemical Letters, 2024, 35(4): 108672-. doi: 10.1016/j.cclet.2023.108672
11. [11]
  Jin Wang , Xiaoyan Pan , Junyu Zhang , Qingqing Zhang , Yanchen Li , Weiwei Guo , Jie Zhang . Active molecule-based theranostic agents for tumor vasculature normalization and antitumor efficacy. Chinese Chemical Letters, 2024, 35(8): 109187-. doi: 10.1016/j.cclet.2023.109187
12. [12]
  Xing Tian , Di Wu , Wanheng Wei , Guifu Dai , Zhanxian Li , Benhua Wang , Mingming Yu . A lipid droplets-targetable fluorescent probe for polarity detection in cells of iron death, inflammation and fatty liver tissue. Chinese Chemical Letters, 2024, 35(6): 108912-. doi: 10.1016/j.cclet.2023.108912
13. [13]
  Jiangshan Xu , Weifei Zhang , Zhengwen Cai , Yong Li , Long Bai , Shaojingya Gao , Qiang Sun , Yunfeng Lin . Tetrahedron DNA nanostructure/iron-based nanomaterials for combined tumor therapy. Chinese Chemical Letters, 2024, 35(11): 109620-. doi: 10.1016/j.cclet.2024.109620
14. [14]
  Hui Zhang , Rong Feng , Wanyi Yu , Hongbei Wei , Tianhong Wu , Peng Zhang , Wenhai Bian , Xin Li , Di Gao , Guojun Weng , Zhe Yang , Tony D. James , Xiaolong Sun . Evaluating the global thiols redox state in living cells using a reducing sulfur species responsive fluorescence switching platform. Chinese Chemical Letters, 2025, 36(4): 110528-. doi: 10.1016/j.cclet.2024.110528
15. [15]
  Jiayu Zeng , Minhui Liu , Ting Yang , Jia Huang , Songjiao Li , Wanting Zhang , Dan Cheng , Longwei He , Jia Zhou . Two-dimensional design strategy to construct smart dual-responsive fluorescent probe for the precise tracking of ischemic stroke. Chinese Chemical Letters, 2025, 36(5): 110166-. doi: 10.1016/j.cclet.2024.110166
16. [16]
  Peng Gao , Yuanyuan Chen , Qianlin He , Xue Liu , Echuan Tan , Zhiqiang Yu , Hui Wang . Highly efficient adoptive cell therapy of metastatic triple negative breast cancer with bioactive covalent organic framework-engineered macrophages. Chinese Chemical Letters, 2025, 36(8): 110585-. doi: 10.1016/j.cclet.2024.110585
17. [17]
  Panpan Wang , Hongbao Fang , Mengmeng Wang , Guandong Zhang , Na Xu , Yan Su , Hongke Liu , Zhi Su . A mitochondria targeting Ir(III) complex triggers ferroptosis and autophagy for cancer therapy: A case of aggregation enhanced PDT strategy for metal complexes. Chinese Chemical Letters, 2025, 36(1): 110099-. doi: 10.1016/j.cclet.2024.110099
18. [18]
  Huijie An , Chen Yang , Zhihui Jiang , Junjie Yuan , Zhongming Qiu , Longhao Chen , Xin Chen , Mutu Huang , Linlang Huang , Hongju Lin , Biao Cheng , Hongjiang Liu , Zhiqiang Yu . Luminescence-activated Pt(Ⅳ) prodrug for in situ triggerable cancer therapy. Chinese Chemical Letters, 2024, 35(7): 109134-. doi: 10.1016/j.cclet.2023.109134
19. [19]
  Lintao Wu , Yujia Meng , Xumei Zheng , Yiqiao Bai , Chun Han , Zhijun Wang , Jie Yang , Xiaobi Jing , Yong Yao . Pillar[5]arene based prodrug as a GSH-responsive SO₂ nanogenerator for effective gas cancer therapy. Chinese Chemical Letters, 2025, 36(9): 110808-. doi: 10.1016/j.cclet.2024.110808
20. [20]
  Yixin Sun , Keke Yu , Xiuchun Guo , Lanlan Zong , Zhonggui He , Xiaohui Pu . Three-in-one reduction and acid-ignited micelles amplify antitumor efficacy via precise synergistic delivery of paclitaxel and naringenin. Chinese Chemical Letters, 2025, 36(6): 110393-. doi: 10.1016/j.cclet.2024.110393

Get Citation

PDF

XML

Metrics

PDF Downloads(2)
Abstract views(992)
HTML views(28)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142