Tubular scaffold made by gelatin/polylactic acid nanofibers for breast ductal carcinoma in situ tumor modeling

Abstract

Ductal carcinoma in situ (DCIS), the outcome of abnormal cells inside a breast milk duct, has a twenty percent prevalence in females with breast cancer. Providing an appropriate DCIS model is critical to study the natural complexity of tumor tissues and cell-cell interactions and treating them. To this end, we designed and developed a biodegradable tubular 3D scaffold made of core-shell nanofibers obtained through emulsion electrospinning. The results showed that the nanofibers with 16.9 wt.% gelatin (as a core) and 83.1 wt.% polylactic acid (PLA; as a shell) unveiled a uniform porous structure with a nanofiber size of around 440 nm. The fabricated tubular 3D scaffold by these nanofibers had an outer and inner diameter of 900 and 416 μm, respectively, in the range of natural ductal carcinoma. Cellular studies showed that the MCF-7 breast cancer cells could well attach and spread out on the scaffold's inside and outside surface, confirming their potential applicability for DCIS modeling in drug screening, drug discovery, and drug efficacy before any pre-clinical studies. Furthermore, as an additional functionality, the scaffold's potency for a drug delivery platform was assessed by loading anticancer docetaxel (DTX) drug on the scaffold, followed by the investigation of in vitro drug release kinetic. The results unfolded a pH-dependency of the scaffold for DTX release. So, the drug release was intensified at pH 6.5 rather than pH 7.4, making it a suitable platform for intensive drug delivery to tumor tissues with acidic environment. In the following, the potential of the prepared tubular scaffold in local drug delivery was studied in vitro in a designed hollow agarose culture media. The released DTX from the DTX-loaded tubular scaffold eradicated MFC-7 cells intensively in comparison with the DTX-free tubular scaffold confirming its capability of local chemotherapy to avoid any side effects of anticancer drugs. In other words, this ability makes these scaffolds a promising candidate for transplanting at the surgery site to reduce the probability of tumor recurrence through localized chemotherapy.