Citation: 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[J]. Chinese Chemical Letters, ;2024, 35(7): 109134. doi: 10.1016/j.cclet.2023.109134 shu

Luminescence-activated Pt(Ⅳ) prodrug for in situ triggerable cancer therapy

Huijie An ^{a, 1} ,
Chen Yang ^{a, 1} ,
Zhihui Jiang ^{a, 1} ,
Junjie Yuan ^b ,
Zhongming Qiu ^c ,
Longhao Chen ^a ,
Xin Chen ^a ,
Mutu Huang ^a ,
Linlang Huang ^a ,
Hongju Lin ^a ,
Biao Cheng ^{a, *,} ,
Hongjiang Liu ^{d, *,} ,
Zhiqiang Yu ^{e, *,}

a.
General Hospital of Southern Theatre Command, PLA, Guangzhou 510010, China
b.
The 925th Hospital of The Chinese People's Liberation Army, Guiyang 550025, China
c.
The 903rd Hospital of The People's Liberation Army, Hangzhou 310007, China
d.
The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China
e.
The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital), Dongguan 523018, China

chengbiaocheng@163.com

willliu0414@163.com

zhiqiang.yu.1@asu.edu

Received Date: 27 July 2023
Revised Date: 19 September 2023
Accepted Date: 20 September 2023
Available Online: 21 September 2023

Figures(5)

Anticancer platinum prodrugs that can be controllably activated are highly desired for personalized precision medicine and patient compliance in cancer therapy. However, the clinical application of platinum(Ⅳ) prodrugs (Pt(Ⅳ)) is restricted by tissue penetration of external irradiation. Here, we report a novel Pt(Ⅳ) activation strategy based on endogenous luminescence of tumor microenvironment responsiveness, which completely circumvents the limitation of external irradiation. The designed Pt(Ⅳ)Lu, a mixture of trans, trans, trans-[Pt(N₃)₂(OH)₂(py)₂] and luminol (Lu), has controllable activation property: it remains inert in reductant environment and normal tissues, but under tumor microenvironment, Lu will be oxidized to produce blue luminescence, which rapidly reduce Pt(Ⅳ) to Pt(Ⅱ) without the need of any external activator. Pt(Ⅳ)Lu shows excellent responsive antitumor ability both in vitro and in vivo. Compared to cisplatin, the median lethal dose in BALB/c mice increased by an order of magnitude. Our results suggest that Pt(Ⅳ)Lu exhibits highly controllable activation property, superior antitumor activity, and good biosafety, which may provide a novel strategy for the design of platinum prodrugs.
- Tumor microenvironment,
- Endogenous luminescence,
- Platinum(Ⅳ) prodrug,
- Activation strategy,
- Antitumor,
- Biosafety
1. [1]
  S. Ghosh, Bioorg. Chem. 88 (2019) 102925. doi: 10.1016/j.bioorg.2019.102925
2. [2]
  C. Zhang, C. Xu, X. Gao, et al., Theranostics 12 (2022) 2115–2132. doi: 10.7150/thno.69424
3. [3]
  T.C. Johnstone, K. Suntharalingam, S.J. Lippard, Chem. Rev. 116 (2016) 3436–3486. doi: 10.1021/acs.chemrev.5b00597
4. [4]
  S. Zhang, X. Wang, Z. Guo, Rational design of anticancer platinum(Ⅳ) prodrugs, in: P.J. Sadler, R. van Eldik (Eds. ), Advances in Inorganic Chemistry, Academic Press, Pittsburgh, 2020, pp. 149–182.
5. [5]
  N.J. Farrer, J.A. Woods, L. Salassa, et al., Angew. Chem. Int. Ed. 49 (2010) 8905–8908. doi: 10.1002/anie.201003399
6. [6]
  Q. Chen, Y. Yang, X. Lin, et al., Chem. Commun. 54 (2018) 5369–5372. doi: 10.1039/c8cc02791a
7. [7]
  S. He, C. Li, Q. Zhang, et al., ACS Nano 12 (2018) 7272–7281. doi: 10.1021/acsnano.8b03476
8. [8]
  R. Weissleder, Nat. Biotechnol. 19 (2001) 316–317. doi: 10.1038/86684
9. [9]
  Z. Wang, N. Wang, S.C. Cheng, et al., Chem 5 (2019) 3151–3165. doi: 10.1016/j.chempr.2019.08.021
10. [10]
  Z. Deng, N. Wang, Y. Liu, et al., J. Am. Chem. Soc. 142 (2020) 7803–7812. doi: 10.1021/jacs.0c00221
11. [11]
  D. Zhou, J. Guo, G.B. Kim, et al., Adv. Healthc. Mater. 5 (2016) 2493–2499. doi: 10.1002/adhm.201600470
12. [12]
  Y. Min, J. Li, F. Liu, et al., Angew. Chem. Int. Ed. 53 (2014) 1012–1016. doi: 10.1002/anie.201308834
13. [13]
  Y. Dai, H. Xiao, J. Liu, et al., J. Am. Chem. Soc. 135 (2013) 18920–18929. doi: 10.1021/ja410028q
14. [14]
  D. Jia, X. Ma, Y. Lu, et al., Chin. Chem. Lett. 32 (2021) 162–167. doi: 10.1016/j.cclet.2020.11.052
15. [15]
  C. Hu, Y. Song, Y. Zhang, et al., Acta Pharm. Sin. B 13 (2023) 2176–2187. doi: 10.1016/j.apsb.2023.02.009
16. [16]
  S. Luo, C. Liang, Q. Zhang, et al., Chin. Chem. Lett. 34 (2023) 107666. doi: 10.1016/j.cclet.2022.07.009
17. [17]
  T. Li, Y. Zhang, J. Zhu, et al., Adv. Mater. 35 (2023) e2210201. doi: 10.1002/adma.202210201
18. [18]
  H.S. Alshetaiwi, S. Balivada, T.B. Shrestha, et al., J. Photochem. Photobiol. B 127 (2013) 223–228. doi: 10.1016/j.jphotobiol.2013.08.017
19. [19]
  H. Zheng, C. Yuan, J. Cai, et al., J. Nanobiotechnol. 20 (2022) 134. doi: 10.1186/s12951-022-01346-4
20. [20]
  N. Zhang, K.P. Francis, A. Prakash, et al., Nat. Med. 19 (2013) 500–505. doi: 10.1038/nm.3110
21. [21]
  X. Xu, H. An, D. Zhang, et al., Sci. Adv. 5 (2019) eaat2953. doi: 10.1126/sciadv.aat2953
22. [22]
  H. An, C. Guo, D. Li, et al., ACS Appl. Mater. Interfaces 12 (2020) 17230–17243. doi: 10.1021/acsami.0c01413
23. [23]
  T.P. Szatrowski, C.F. Nathan, Cancer Res. 51 (1991) 794–798.
1. [1]
  Li Fu , Ziye Su , Shuyang Wu , Yanfen Cheng , Chuan Hu , Jinming Zhang . Redox-responsive hyaluronic acid-celastrol prodrug micelles with glycyrrhetinic acid co-delivery for tumor combination therapy. Chinese Chemical Letters, 2025, 36(5): 110227-. doi: 10.1016/j.cclet.2024.110227
2. [2]
  Yunkang Tong , Haiqiao Huang , Haolan Li , Mingle Li , Wen Sun , Jianjun Du , Jiangli Fan , Lei Wang , Bin Liu , Xiaoqiang Chen , Xiaojun Peng . Cooperative bond scission by HRP/H₂O₂ for targeted prodrug activation. Chinese Chemical Letters, 2024, 35(12): 109663-. doi: 10.1016/j.cclet.2024.109663
3. [3]
  Fengyun Li , Zerong Pei , Shuting Chen , Gen li , Mengyang Liu , Liqin Ding , Jingbo Liu , Feng Qiu . Multifunctional nano-herb based on tumor microenvironment for enhanced tumor therapy of gambogic acid. Chinese Chemical Letters, 2024, 35(5): 108752-. doi: 10.1016/j.cclet.2023.108752
4. [4]
  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
5. [5]
  Zhiqiang Cui , Dongxiang Zhang , Yanru Huang , Chunyu Shao , Yiming Zhang , Changliang Sun , Xin-Dong Jiang , Xiaohong Sun , Qinghuan Xiao . Novel 1-phenylethyl-containing aza-BDOIPY for phototherapy and simultaneous monitoring of tumor immune microenvironment reprogramming. Chinese Chemical Letters, 2025, 36(7): 110460-. doi: 10.1016/j.cclet.2024.110460
6. [6]
  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
7. [7]
  Boyuan Liu , Zixu Liu , Ping Wang , Yu Zhang , Haibing He , Tian Yin , Jingxin Gou , Xing Tang . Nanomedicine-based targeting delivery systems for peritoneal cavity localized therapy: A promising treatment of ovarian cancer and its peritoneal metastasis. Chinese Chemical Letters, 2025, 36(6): 110229-. doi: 10.1016/j.cclet.2024.110229
8. [8]
  Zhi-Lin Wu , Rong-Nan Yi , Chunlin Zhuang . Electrochemical synthesis strategy for the development of antitumor selenoheterocyclic compounds. Chinese Chemical Letters, 2025, 36(10): 111408-. doi: 10.1016/j.cclet.2025.111408
9. [9]
  Hu Wu , Ge Cao , Mingyang Liu , Hainan Xu , Meng Li , Hanwei Huang , Yujie Liu , Xu Zhao , Xifeng Qin , Onder Ergonul , Füsun Can , Funan Liu , Zhiqing Pang , Jiaming Zhu . Tumor cell membrane biomimetic liposomes-coated oncolytic viruses to target the homotypic tumor and augment the antitumor efficacy. Chinese Chemical Letters, 2025, 36(7): 110493-. doi: 10.1016/j.cclet.2024.110493
10. [10]
  Yongjuan Li , Rongrong Zhu , Yichen Guo , Yayun Wang , Rong Ma , Kunru Ma , Yongxing Zhao , Weijing Yang . Sequential-gated transformable nanoprodrug potentiates antitumor immunity through TME modulation and STING activation. Chinese Chemical Letters, 2025, 36(9): 110704-. doi: 10.1016/j.cclet.2024.110704
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]
  Fa Wang , Yu Chen , Hui Chao . Ruthenium(II) Complexes as Photoactivated Chemo-Prodrugs for Hypoxic Tumor Therapy. University Chemistry, 2025, 40(7): 200-212. doi: 10.12461/PKU.DXHX202410024
13. [13]
  Zimo Shen , Tongwei Zhang , Zhiyi Zhu , Zonghao Gong , Qing Feng , Jinyi Yang , Zhen Li , Min Liu , Wei Qi . From Alkaloid to Anticancer Agent: The Transformative Journey of Camptothecin. University Chemistry, 2025, 40(10): 161-165. doi: 10.12461/PKU.DXHX202411027
14. [14]
  Jiahao Zeng , Hui Chao . 诱导程序性细胞死亡的金属抗肿瘤药物研究. University Chemistry, 2025, 40(6): 145-159. doi: 10.12461/PKU.DXHX202406019
15. [15]
  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. Chinese Chemical Letters, 2024, 35(10): 109538-. doi: 10.1016/j.cclet.2024.109538
16. [16]
  Hao Sun , Shengke Li , Qian Liu , Minzan Zuo , Xueqi Tian , Kaiya Wang , Xiao-Yu Hu . Supramolecular prodrug vesicles for selective antimicrobial therapy employing a chemo-photodynamic strategy. Chinese Chemical Letters, 2025, 36(3): 109999-. doi: 10.1016/j.cclet.2024.109999
17. [17]
  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
18. [18]
  Honghao Sun , Huimin Zhao , Ronghui Yin , Chenxi Zhou , Ming Wu , Yueyang Deng , Zhanwei Zhou , Minjie Sun . Injectable hydrogel-based tumor vaccine with fibrotic tumor immune microenvironment remodeling to prevent breast cancer postoperative recurrence and metastases. Chinese Chemical Letters, 2025, 36(5): 110067-. doi: 10.1016/j.cclet.2024.110067
19. [19]
  Tingting Hu , Chao Shen , Xueyan Wang , Fengbo Wu , Zhiyao He . Tumor microenvironment-sensitive polymeric nanoparticles for synergetic chemo-photo therapy. Chinese Chemical Letters, 2024, 35(11): 109562-. doi: 10.1016/j.cclet.2024.109562
20. [20]
  Wenbin Zhou , Yafei Gao , Xinyu Feng , Yanqing Zhang , Cong Yang , Lanxi He , Fenghe Zhang , Xiaoguang Li , Qing Li . Biomimetic nanoplatform integrates FRET-enhanced photodynamic therapy and chemotherapy for cascaded revitalization of the tumor immune microenvironment in OSCC. Chinese Chemical Letters, 2025, 36(1): 109763-. doi: 10.1016/j.cclet.2024.109763

Get Citation

PDF

XML

Metrics

PDF Downloads(5)
Abstract views(1039)
HTML views(20)

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