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<p>Breast cancer (BC) is the second most prevalent form of cancer worldwide. Minimal residual disease (MRD), the small population of tumor cells left near the tumor after surgical ablation, leads to tumor recurrence. Overexpression of efflux proteins makes the MRD resistant to taxane therapy. Paclitaxel (PTX) is the first-line chemotherapeutic agent in BC. However, prolonged administration results in the emergence of multidrug resistance due to the expression of P-glycoprotein and metastasis. Simvastatin (SIM), a cholesterol synthesis inhibitor, has shown tremendous anticancer potential in a plethora of cancers along with pronounced anti-invasive activity and P-glycoprotein downregulation. In order to prevent untoward adverse effects, nanofiber implants loaded with both drugs were fabricated with sustained release for up to 7&#xa0;days. Enhanced apoptosis was observed for drugs post-incorporation into the nanofibers with prominent anti-invasive activity. The incorporation of simvastatin resulted in P-glycoprotein efflux reversal of paclitaxel as evidenced by the rhodamine 123 assay and PTX sensitivity. The transwell invasion assay reduced the number of invading cells post-fiber treatment. Thus, we conclude that PTX- and SIM-loaded nanofibers could be a viable therapeutic alternative to prevent post-surgical tumor recurrence and cancer cell invasion.</p> Graphical Abstract <p></p>

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Establishment and Evaluation of Paclitaxel and Simvastatin-Laden Nanofibers for Post-surgical Tumor Recurrence in Breast Cancer

  • 期刊论文

  • 发表日期：

    2025年5月21日

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  • Paras Famta,
  • Saurabh Shah,
  • Ganesh Vambhurkar,
  • Rahul Kumar,
  • Giriraj Pandey,
  • Gurpreet Singh,
  • Suraj Wagh,
  • Dilip Kumar Arya,
  • Shubham Kanaujiya,
  • Abhishek Sharma,
  • Sajja Bhanu Prasad,
  • Akshay Shinde,
  • Sachin Chandankar,
  • Swapnil Shinde,
  • Anamika Sharma,
  • P. S. Rajinikanth,
  • Nitin Pal Kalia,
  • Amit Asthana,
  • Saurabh Srivastava

摘要

Breast cancer (BC) is the second most prevalent form of cancer worldwide. Minimal residual disease (MRD), the small population of tumor cells left near the tumor after surgical ablation, leads to tumor recurrence. Overexpression of efflux proteins makes the MRD resistant to taxane therapy. Paclitaxel (PTX) is the first-line chemotherapeutic agent in BC. However, prolonged administration results in the emergence of multidrug resistance due to the expression of P-glycoprotein and metastasis. Simvastatin (SIM), a cholesterol synthesis inhibitor, has shown tremendous anticancer potential in a plethora of cancers along with pronounced anti-invasive activity and P-glycoprotein downregulation. In order to prevent untoward adverse effects, nanofiber implants loaded with both drugs were fabricated with sustained release for up to 7 days. Enhanced apoptosis was observed for drugs post-incorporation into the nanofibers with prominent anti-invasive activity. The incorporation of simvastatin resulted in P-glycoprotein efflux reversal of paclitaxel as evidenced by the rhodamine 123 assay and PTX sensitivity. The transwell invasion assay reduced the number of invading cells post-fiber treatment. Thus, we conclude that PTX- and SIM-loaded nanofibers could be a viable therapeutic alternative to prevent post-surgical tumor recurrence and cancer cell invasion.

Graphical Abstract