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
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沈阳化工大学材料科学与工程学院沈阳 110142