Citation: Shuxin Liu, Jinjuan Ma, Aiguo Wang, Nan Zheng. Decomposable and sono-enzyme co-triggered poly(sonosensitizers) for precise and hypotoxic sonodynamic therapy[J]. Chinese Chemical Letters, ;2025, 36(4): 110032. doi: 10.1016/j.cclet.2024.110032 shu

Decomposable and sono-enzyme co-triggered poly(sonosensitizers) for precise and hypotoxic sonodynamic therapy

Shuxin Liu ^a ,
Jinjuan Ma ^b ,
Aiguo Wang ^b ,
Nan Zheng ^{a, *,}

a.
School of Chemical Engineering, Cancer Hospital of Dalian University of Technology, Dalian University of Technology, Dalian 116023, China
b.
Department of Comparative Medicine Laboratory Animal Center, Dalian Medical University, Dalian 116000, China

nzheng@dlut.edu.cn

Received Date: 28 March 2024
Revised Date: 15 May 2024
Accepted Date: 20 May 2024
Available Online: 21 May 2024

Figures(5)

A decomposable and sono-enzyme co-triggered nanoparticle (pTCP-CR NP) with “AND gate” logic was synthesized, combining a meso‑carboxyl-porphyrin-based sonosensitizer (5,10,15,20-tetrakis(carboxyl)porphyrin, TCP) and a thiophenyl-croconium (2,5-bis[(2-(2-(2-hydroxyethoxy)ethoxy)ethyl-4-carboxylate-piperidylamino)thiophenyl]-croconium, CR) via ester groups. TCP releases carbon monoxide (CO) under ultrasound (US) irradiation, offering both sonodynamic and gas therapy. CR decomposes into stronger reactive oxygen species (ROS) compared to oxygen-based radicals. The Förster resonance energy transfer (FRET) effect between TCP and CR inhibits ROS and CO generation until triggered by tumor cell overexpressed carboxylesterase (CEs). pTCP-CR NPs “AND gate” logic ensures activation only in the presence of both CEs and US, targeting tumor cells while safety in normal tissues. The ROS and CO generation abilities, as well as the releasing of SO₄^•− have been systemically examined. pTCP-CR can be thoroughly decomposed into low-toxic molecules post the treatment, showing the safety with negligible phototoxic reactions. In vivo anti-cancer therapy has been evaluated using mice bearing hepatocellular carcinoma.
- “AND gate” logic,
- Hypotoxic sonodynamic therapy,
- Ultrasound and enzyme co-trigger,
- Sulfate radicals,
- Förster resonance energy transfer effect
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