A conjugated 2D covalent organic framework as a drug delivery vehicle towards triple negative breast cancer malignancy

Cancer, one of the deadliest diseases for both sexes, has always demanded updated treatment strategies with time. Breast cancer is responsible for the highest mortality rate among females worldwide and requires treatment with advanced regimens due to the higher probability of breast cancer cells to develop drug cytotoxicity followed by resistance. Covalent organic framework (COF) materials with ordered nanoscale porosity can serve as drug delivery vehicles due to their biocompatible nature and large internal void spaces. In this research work, we have employed a novel biocompatible COF, TRIPTA, as a drug delivery carrier towards breast cancer cells. It served as a drug delivery vehicle for cisplatin in triple negative breast cancer (TNBC) cells. We have checked the potency of TRIPTA in combating the proliferation of metastatic TNBC cells. Our results revealed that cisplatin loaded over TRIPTA-COF exhibited a greater impact on the CD44(+)/CD24(-) cancer stem cell niche of breast cancer. Retarded migration of cancer cells has also been observed with the dual treatment of TRIPTA and cisplatin compared to that of cisplatin alone. Epithelial-mesenchymal transition (EMT) has also been minimized by the combinatorial treatment of cisplatin carried by the carrier material in comparison to cisplatin alone. The epithelial marker E-cadherin is significantly increased in cells treated with cisplatin together with the carrier COF, and the expression of mesenchymal markers such as N-cadherin is lower. The transcriptional factor Snail has been observed under the same treatment. The carrier material is also internalized by the cancer cells in a time-dependent manner, suggesting that the organic carrier can serve as a specific drug delivery vehicle. Our experimental results suggested that TRIPTA-COF can serve as a potent nanocarrier for cisplatin, showing higher detrimental effects on the proliferation and migration of TNBC cells by increasing the cytotoxicity of cisplatin.

Automated summary

In this research, a novel biocompatible COF material, TRIPTA, is used as a drug delivery carrier for cisplatin to combat the proliferation and migration of TNBC cells. The study demonstrates that TRIPTA-COF can serve as a potent nanocarrier, showing higher detrimental effects on TNBC cells by increasing the cytotoxicity of cisplatin and minimizing epithelial-mesenchymal transition.