Citation: Ruohan Xiao, Hongmei Liu, Jiaxue Wen, Xiaoxiao Shi, Junjie Zhang, Zhi-Jun Sun, Zhigang Xu. Dual-responsive polygossypol supramolecular prodrugs combined with oncolytic herpes simplex virus enhance anti-triple-negative breast cancer therapy[J]. Chinese Chemical Letters, ;2026, 37(11): 112206. doi: 10.1016/j.cclet.2025.112206 shu

Dual-responsive polygossypol supramolecular prodrugs combined with oncolytic herpes simplex virus enhance anti-triple-negative breast cancer therapy

Ruohan Xiao ^{a, 1} ,
Hongmei Liu ^{a, 1} ,
Jiaxue Wen ^a ,
Xiaoxiao Shi ^{a, b, *,} ,
Junjie Zhang ^c ,
Zhi-Jun Sun ^c ,
Zhigang Xu ^{a, b, *,}

a.
Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, School of Materials and Energy, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, China
b.
Yibin Academy of Southwest University, Yibin 644000, China
c.
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430079, China

xxshi7@swu.edu.cn

zgxu@swu.edu.cn

Received Date: 16 September 2025
Revised Date: 1 December 2025
Accepted Date: 2 December 2025
Available Online: 3 December 2025

Figures(4)

Oncolytic virus therapy represents a promising avenue in the battle against cancer, however, its efficacy is frequently constrained by the hostile tumor microenvironment and insufficient therapeutic responses. Herein, we engineered a pH/glutathione dual-responsive supramolecular prodrug nanomedicine (termed PGPP), derived from gossypol, designed to synergize with oncolytic herpes simplex virus (oHSV) therapy for the treatment of triple-negative breast cancer (TNBC). Our findings revealed that PGPP exhibited remarkable tumor-targeting accumulation and retention, significantly enhancing the cytotoxic potency of gossypol within malignant tissues. Crucially, PGPP effectively disrupted vascular endothelial growth factor (VEGF)-driven angiogenesis, fostering a more permissive milieu for oncolytic viral infiltration. The incorporation of oHSV in turn amplified the antitumor activity of PGPP, promoting cancer cell apoptosis and augmenting immunogenic cell death, ultimately resulting in robust tumor growth inhibition. This coordinated combination strategy-based supramolecular prodrug delivers a powerful blow against TNBC, offering a promising paradigm for future cancer treatments.
- Triple-negative breast cancer (TNBC),
- Oncolytic virotherapy,
- Gossypol supermolecule prodrug,
- Dual-responsive nanomedicine,
- Synergistic therapy
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