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Abstract
The aim of this study was to develop docetaxel (DTX)-loaded poly-d,l-lactide (PDLLA) nanofibers and evaluate their therapeutic effect in preventing local breast cancer recurrence. DTX was incorporated into biodegradable PDLLA nanofibers by electrospinning. The surface morphology of the DTX/PDLLA nanofibers was characterized using scanning electron microscopy and wide angle X-ray diffraction. The in vitro release behavior of DTX from the fiber mats was also studied in detail. The cytotoxicity of DTX/PDLLA nanofibers was evaluated by MTT assay in 4T1 breast cancer cells. Flow cytometry revealed that DTX/PDLLA nanofibers exhibited apoptotic activity in 4T1 cells. In vivo antitumor efficacy of DTX/PDLLA nanofibers was evaluated in BALB/c mice bearing local breast tumors. Locoregional recurrence after primary tumor resection decreased obviously in mice treated with subcutaneously (16.7%) administered DTX-loaded PDLLA nanofibers, compared with the blank PDLLA nanofibers (88.9%), systemic (75.0%) or locally (77.8%) administered DTX and the control group (100%) (p < 0.05). Finally, after subcutaneous transplantation in mice, the DTX/PDLLA scaffolds presented excellent biocompatibility, as exhibited by the minimal presence of inflammatory cells in the region surrounding the scaffolds. Our results suggest that DTX/PDLLA nanofibers could have great potential for clinical application requiring local chemotherapy.
Declaration of interest
This work was financially supported by National Natural Science Foundation (NSFC31222023, NSFC51303203), Luzhou Science and Technology Plan (2013CDLZ-S21) and Distinguished young scholars of Sichuan University (2011SCU04B18).