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<p>Oral squamous cell carcinoma (OSCC) poses a major global health issue, particularly in India, where late-stage diagnoses and high mortality rates are prevalent. Traditional treatment methods, such as surgery, chemotherapy, and radiotherapy, have shown limitations, underscoring the need for more efficient and novel approaches. To address these limitations, we developed innovative nanofiber-based neoadjuvant therapy utilizing disulfiram (DIS) for targeted oral cancer treatment. DIS, a repurposed medication, exhibits strong anticancer effects by suppressing HIF-1α, NF-κB, MMP-2, and MMP-9, and modulating EMT and autophagy. Polycaprolactone (PCL) nanofibers were engineered to provide sustained, localized delivery of DIS, replicating the extracellular matrix to support post-surgical wound healing. Cell culture studies in KB-3–1 oral cancer cells demonstrated a 2.48-fold increase in the ROS production of DIS-loaded nanofibers (DNF) compared to the control group and significant apoptosis, as evidenced by AO/EB staining. Further, flow cytometry revealed that developed DNF induced mitochondria-dependent apoptosis in the oral cancer cell line. Clonogenic assay demonstrated that DNF significantly inhibited colony formation (*** <i>p</i> &lt; 0.001). Finally, western blot analysis showed a downregulation in the expression of <i>BCL-2</i> and upregulation of <i>BAX</i> (<i>p</i> &lt; 0.001, ***), demonstrating apoptosis-mediated cell death in the KB-3–1 cell line. Thus, we conclude that the developed nanofiber approach enables precise, localized drug delivery in the management of oral squamous cell carcinoma.</p> Graphical Abstract <p></p>

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Disulfiram-Encapsulated Poly(caprolactone) Nanofiber Scaffolds for Oral Squamous Cell Carcinoma Management

  • 期刊论文

  • 发表日期：

    2025年9月18日

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  • Giriraj Pandey,
  • Paras Famta,
  • Saurabh Shah,
  • Rahul Kumar,
  • Suraj Wagh,
  • Ganesh Vambhurkar,
  • Anamika Sharma,
  • Abhishek Sharma,
  • Swapnil Shinde,
  • Gurpreet Singh,
  • Sachin Chandankar,
  • Aman Dalal,
  • Nitin Pal Kalia,
  • Amit Asthana,
  • Saurabh Srivastava

摘要

Oral squamous cell carcinoma (OSCC) poses a major global health issue, particularly in India, where late-stage diagnoses and high mortality rates are prevalent. Traditional treatment methods, such as surgery, chemotherapy, and radiotherapy, have shown limitations, underscoring the need for more efficient and novel approaches. To address these limitations, we developed innovative nanofiber-based neoadjuvant therapy utilizing disulfiram (DIS) for targeted oral cancer treatment. DIS, a repurposed medication, exhibits strong anticancer effects by suppressing HIF-1α, NF-κB, MMP-2, and MMP-9, and modulating EMT and autophagy. Polycaprolactone (PCL) nanofibers were engineered to provide sustained, localized delivery of DIS, replicating the extracellular matrix to support post-surgical wound healing. Cell culture studies in KB-3–1 oral cancer cells demonstrated a 2.48-fold increase in the ROS production of DIS-loaded nanofibers (DNF) compared to the control group and significant apoptosis, as evidenced by AO/EB staining. Further, flow cytometry revealed that developed DNF induced mitochondria-dependent apoptosis in the oral cancer cell line. Clonogenic assay demonstrated that DNF significantly inhibited colony formation (*** p < 0.001). Finally, western blot analysis showed a downregulation in the expression of BCL-2 and upregulation of BAX (p < 0.001, ***), demonstrating apoptosis-mediated cell death in the KB-3–1 cell line. Thus, we conclude that the developed nanofiber approach enables precise, localized drug delivery in the management of oral squamous cell carcinoma.

Graphical Abstract