2. Academic Validation
  3. Intranasal delivery of temozolomide and disulfiram in situ gel combined with copper for enhanced glioblastoma therapy

Intranasal delivery of temozolomide and disulfiram in situ gel combined with copper for enhanced glioblastoma therapy

  • Colloids Surf B Biointerfaces. 2025 Jun 24:255:114898. doi: 10.1016/j.colsurfb.2025.114898.
Ying Qu 1,  Jingjing Zhao 2,  Long Ma 3,  Xue Wang 4,  Feifei Sun 5,  Yizhe Li 2,  Yihua Wu 3,  Guozhi Zhao 2,  Shijia Liu 5,  Wenqing Ma 2,  Tao Li 6,  Zhongxi Zhao 7
Affiliations

Affiliations

  • 1 Department of Pharmacy, The Second Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Street, Jinan, Shandong 250033, China.
  • 2 Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Cultural West Road, Jinan, Shandong 250012, China.
  • 3 The Testing Center of Shandong Bureau of China Metallurgical Geology Bureau, 14 Shanshi East Road, Jinan, Shandong 250100, China.
  • 4 Shandong Institute for Food and Drug Control, 2749 Xinluo Street, Jinan, Shandong 250101, China.
  • 5 Department of General Surgery, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, 107 Cultural West Road, Jinan, Shandong 250012, China.
  • 6 Department of General Surgery, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, 107 Cultural West Road, Jinan, Shandong 250012, China. Electronic address: litao7706@163.com.
  • 7 Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Cultural West Road, Jinan, Shandong 250012, China. Electronic address: zxzhao@sdu.edu.cn.
PMID: 40592114 DOI: 10.1016/j.colsurfb.2025.114898
Abstract

Combination therapies show promise for glioblastoma (GBM) treatment, however, insufficient drug accumulation in the brain and significant toxic side effects continue to pose critical challenges to therapeutic efficacy. Here, we report an intranasal ion-sensitive hydrogel (IHG) platform for efficient co-delivery of TMZ and disulfiram (DSF) to GBM via the nose-to-brain pathway. The optimized IHG formulation demonstrates superior gelation properties, sustained drug release, and enhanced brain accumulation, achieving remarkable drug targeting efficiency (468.9 %) and direct transport percentage (80.3 %). Within the tumor microenvironment, in situ-generated TMZ and the chelation product of DSF and copper ions (CuET) synergistically induce DNA damage and Apoptosis, thereby enhancing tumor cell sensitivity to TMZ. Furthermore, tdIHG+Cu induces robust immunogenic cell death, stimulates CXCL10 release, mediates dendritic cell maturation, and promotes CD8+ T cell infiltration, thereby establishing a potent antitumor immune response. This approach not only demonstrates superior therapeutic efficy against GBM progression through enhanced intracranial drug accumulation and optimized drug ratios, but also minimizes systemic toxicity via localized delivery. Our findings offer a potentially clinical translatable strategy worth further investigation.

Keywords

Antitumor immune; Disulfiram+Cu; Glioblastoma; Nose-to-brain drug delivery; Temozolomide.

Figures
Products
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  • HY-D0938
    99.01%, Cell Proliferation Fluorescent Probe