Exploration of Multi-layered Nanofiber Adjuvant Implants of Doxorubicin and Resveratrol to Prevent Post-Surgery Tumor Recurrence and Invasion

Abstract

Tumor-free survival post-surgical ablation is not durable due to tumor recurrence and metastasis in breast cancer patients. Studies have reported that trauma-prone sites are most vulnerable to the seeding of disseminated tumor cells (DTC) and ultimately tumor recurrence. We have developed Doxorubicin (DOX) and Resveratrol (RES) loaded nanofibers (NFs) to be used as adjuvant implants after surgical removal of the breast tumor. The electrospinning technique was employed to develop the NFs. Cell line evaluations showed synergistic activity of the drug combination on the MDA-MB-231 metastatic cell line. The cell cycle analysis revealed that the DOX and RES arrested the cell cycle in the G2/M and G0/G1 phases, respectively. The scratch assay exhibited that the co-delivery of RES prevented the invasive potential of the MDA-MB-231 cell line. The sustained nature of drug release from the NFs decreased DOX-induced necrotic cell death. The co-delivery of RES and DOX promoted apoptotic cell death in the MDA-MB-231 cell line. Thus, we conclude that the DOX and RES-loaded NFs can be employed as post-surgery adjuvant implants to check tumor recurrence and metastasis.