2. Academic Validation
  3. Folic acid-modified disulfiram/Zn-IRMOF3 nanoparticles for oral cancer therapy by inhibiting ALDH1A1+ cancer stem cells

Folic acid-modified disulfiram/Zn-IRMOF3 nanoparticles for oral cancer therapy by inhibiting ALDH1A1+ cancer stem cells

  • Biomater Adv. 2022 Aug:139:213038. doi: 10.1016/j.bioadv.2022.213038.
Jiasen Cui 1,  Weitao Li 2,  Wenhuan Bu 3,  Jinhui Liu 4,  Xi Chen 1,  Xuewen Li 1,  Chunran Liu 1,  Lin Meng 5,  Mingli Chen 6,  Hongchen Sun 7,  Jianhua Wang 4
Affiliations

Affiliations

  • 1 School and Hospital of Stomatology, Department of Oral Pathology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang 110001, China.
  • 2 Research Center for Analytical Sciences, Department of Chemistry, College of Sciences, Northeastern University, P.O. Box 332, Shenyang 110819, China; College of Chemistry and Chemical Engineering, Xingtai University, Xingtai, Hebei 054001, China.
  • 3 School and Hospital of Stomatology, Department of Dental Materials, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang 110001, China.
  • 4 Research Center for Analytical Sciences, Department of Chemistry, College of Sciences, Northeastern University, P.O. Box 332, Shenyang 110819, China.
  • 5 Department of Oral Pathology, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, School and Hospital of Stomatology, Jilin University, Changchun, China.
  • 6 Research Center for Analytical Sciences, Department of Chemistry, College of Sciences, Northeastern University, P.O. Box 332, Shenyang 110819, China. Electronic address: [email protected].
  • 7 School and Hospital of Stomatology, Department of Oral Pathology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang 110001, China. Electronic address: [email protected].
PMID: 35908474 DOI: 10.1016/j.bioadv.2022.213038
Abstract

The repurposing of old drugs can reduce the cost of drug development and speed up the availability of drugs for clinical use. Disulfiram (DSF) is an approved drug for alcohol abuse. In recent years, it has been established that DSF exerts an antitumor effect via targeted inhibition of ALDH1+ Cancer Stem Cells (CSCs). However, due to its metal ion dependence, easy hydrolysis and low availability, the clinical application of DSF is limited. Previous studies have also shown that Zn2+ can inhibit CSCs. Accordingly, we developed a novel metal organic framework (IRMOF3)-Zn2+, and DSF was incorporated in the IRMOF3. Folic acid (FA) was subsequently loaded on the surface yielding IRMOF3 (IRMOF3-DSF-FA) for targeted therapy of tumors. The nanoscale IRMOF3-DSF-FA exhibited a high loading capacity, good biocompatibility and strong cell uptake capacity, which could provide metal ions, target tumor tissues and inhibit ALDH1+ CSCs. In vivo experiments showed that IRMOF3-DSF-FA could significantly inhibit the growth of CSCs and tumors, with no significant vital organ damage during treatment. Accordingly, IRMOF3-DSF-FA has great prospects for application as a DSF carrier, opening new horizons for targeted therapy of oral Cancer.

Keywords

Disulfiram; Mental-organic frameworks; Oral squamous cell carcinoma; Tumor therapy.

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