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Disulfiram-loaded copper sulfide nanoparticles for potential anti-glioma therapy
Qing-Hua Lan1, Chu-Chu Du1, Run-Jie Yu2
1School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China; Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
International Journal of Pharmaceutics
|August 9, 2021
Summary
Transferrin-modified disulfiram/copper sulfide nanocomplexes show potent anti-glioma therapy. This targeted approach leverages pH-triggered drug release and photothermal ablation for significant tumor suppression.
Area of Science:
- Nanomedicine
- Oncology
- Materials Science
Background:
- Disulfiram (DSF) is a copper (Cu2+)-dependent antitumor agent.
- Glioma therapy requires targeted drug delivery and effective treatment modalities.
- Copper sulfide (CuS) nanoparticles offer potential as photothermal agents and drug carriers.
Purpose of the Study:
- To develop and evaluate a transferrin (Tf)-modified disulfiram/copper sulfide (Tf-DSF/CuS) nanocomplex for targeted glioma therapy.
- To investigate the pH-triggered release of Cu2+ and its role in DSF's cytotoxic activity.
- To assess the combined efficacy of targeted drug delivery, photothermal therapy, and drug release in vivo.
Main Methods:
- Synthesis of Tf-DSF/CuS nanocomplexes via metal-chelation of DSF onto CuS nanoparticles, followed by Tf modification.
- In vitro cytotoxicity assays to evaluate the efficacy of Tf-DSF/CuS at different pH levels.
- Ultrasound-targeted microbubble destruction (UTMD) for targeted delivery of Tf-DSF/CuS to orthotopic glioma models.
- In vivo tumor growth inhibition assessment using MRI and pathological examination, combined with 808 nm laser irradiation for photothermal therapy.
Main Results:
- Tf-DSF/CuS nanocomplexes exhibited significant in vitro cytotoxicity, dependent on pH-triggered Cu2+ release and DSF activation.
- UTMD facilitated highly selective accumulation of Tf-DSF/CuS in glioma tumors.
- Tf-DSF/CuS demonstrated remarkable in vivo tumor growth suppression (~85% inhibition) with minimal compromise to CuS photothermal properties.
- Photothermal ablation therapy using Tf-DSF/CuS showed significant efficacy both in vitro and in vivo.
Conclusions:
- Tf-DSF/CuS nanocomplexes represent a promising targeted therapeutic strategy for glioma.
- The pH-triggered release mechanism enhances DSF's anti-glioma activity.
- Combination therapy involving targeted delivery, drug release, and photothermal ablation offers a potent approach for effective glioma treatment.
