2. Academic Validation
  3. Sertaconazole-repurposed nanoplatform enhances lung cancer therapy via CD44-targeted drug delivery

Sertaconazole-repurposed nanoplatform enhances lung cancer therapy via CD44-targeted drug delivery

  • J Exp Clin Cancer Res. 2023 Jul 29;42(1):188. doi: 10.1186/s13046-023-02766-2.
Ruolan Liu # 1,  Qiong Li # 2,  Siyuan Qin # 2,  Ling Qiao 1,  Mei Yang 2,  Shanshan Liu 3,  Edouard C Nice 4,  Wei Zhang 5 6,  Canhua Huang 1 2,  Shaojiang Zheng 7,  Wei Gao 8
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
  • 2 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
  • 3 School of Pharmacy, Zunyi Medical University, Zunyi, 563000, China.
  • 4 Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia.
  • 5 West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • 6 Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China.
  • 7 Hainan Cancer Center of The First Affiliated Hospital, Key Laboratory of Tropical Cardiovascular Diseases Research of Hainan Province, Hainan Women and Children's Medical Center, Hainan Medical University, Haikou, 571199, China. [email protected].
  • 8 Clinical Genetics Laboratory, Affiliated Hospital & Clinical Medical College of Chengdu University, Chengdu, 610081, China. [email protected].
  • # Contributed equally.
PMID: 37507782 DOI: 10.1186/s13046-023-02766-2
Abstract

Background: Lung Cancer is one of the most frequent causes of cancer-related deaths worldwide. Drug repurposing and nano-drug delivery systems are attracting considerable attention for improving anti-cancer therapy. Sertaconazole (STZ), an Antifungal agent, has been reported to exhibit cytotoxicity against both normal and tumor cells, and its medical use is limited by its poor solubility. In order to overcome such shortcomings, we prepared a drug-repurposed nanoplatform to enhance the anti-tumor efficiency.

Methods: Nanoplatform was prepared by thin film dispersion. Drug release studies and uptake studies were measured in vitro. Subsequently, we verified the tumor inhibition mechanisms of HTS NPs through Apoptosis assay, immunoblotting and Reactive Oxygen Species (ROS) detection analyses. Antitumor activity was evaluated on an established xenograft lung Cancer model in vivo.

Results: Our nanoplatform improved the solubility of sertaconazole and increased its accumulation in tumor cells. Mechanistically, HTS NPs was dependent on ROS-mediated Apoptosis and pro-apoptotic Autophagy to achieve their excellent anti-tumor effects. Furthermore, HTS NPs also showed strong inhibitory ability in nude mouse xenograft models without significant side effects.

Conclusions: Our results suggest that sertaconazole-repurposed nanoplatform provides an effective strategy for lung Cancer treatment.

Keywords

Drug repurposing; Lung cancer; Nanoparticle; Sertaconazole; Targeted delivery.

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