Citation: Huipeng Li, Xue Yang, Minjie Sun. Self-strengthened cascade-explosive nanogel using host-guest interaction strategy for synergistic tumor treatment[J]. Chinese Chemical Letters, ;2025, 36(8): 110651. doi: 10.1016/j.cclet.2024.110651 shu

Self-strengthened cascade-explosive nanogel using host-guest interaction strategy for synergistic tumor treatment

Huipeng Li ^{a, *,} ,
Xue Yang ^c ,
Minjie Sun ^{b, *,}

a.
Center for Health Science and Engineering, Hebei Key Laboratory of Biomaterials and Smart Theranostics, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin 300131, China
b.
State Key Laboratory of Natural Medicines and Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China
c.
Cultivation and Construction Site of the State Key Laboratory of Intelligent Imaging and Interventional Medicine, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China

lhp@hebut.edu.cn

msun@cpu.edu.cn

Received Date: 19 September 2024
Revised Date: 8 November 2024
Accepted Date: 13 November 2024
Available Online: 14 November 2024

Figures(5)

Despite the considerable potentiality of photodynamic therapy (PDT) in cancer treatment, conventional hydrophobic photosensitizers cause obstacles for in vivo application, while their inert structures are difficult to chemically modify. Additionally, undesirable tumor hypoxia resulting from oxygen consumption also discounts the therapeutic efficacy of PDT. Herein, we developed a self-strengthened nanogel with reactive oxygen species (ROS) trigger-explosive property. IR780 was spontaneous assembled within the conical cavity of cyclodextrin (β-CD) using host-guest interactions, while adjacent IR780 molecules on the dextrin backbone with hydrophobic interaction and π conjugation induced nanogel formation. Simultaneously, hydrophilic compound tirapazamine (TPZ) was incorporated into nanogel for synergistic tumor treatment. The inherent high levels of ROS in tumor can break down boronic ester bond linker of nanogel, initiating its disintegration. Furthermore, our findings indicate the ROS level (including H₂O₂ and ¹O₂) can be transiently enhanced during PDT process at the animal level, which accelerates the explosion of nanogel. Notably, the IR780@β-CD module exhibited enhanced ROS generation efficiency during PDT with the continues explosion of nanogel, which further strengthens nanogel disintegration, tumor phototherapy and cargo releasement. Additionally, the released TPZ is activated under hypoxic conditions after PDT treatment, addressing the limitations of PDT and facilitating multi-synergistic tumor treatment.
- Host-guest interaction,
- Self-strengthening,
- Cascade-explosive nanogel,
- ROS trigger-disassembly,
- Hypoxia-activated chemotherapy
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