In vitro and in vivo investigation of the effect of TRAIL-loaded drug delivery systems on tumors

Objective: TRAIL is a critical protein that functions by impeding the viability of cancerous cells, exhibiting a brief half-life. The development of effective drug delivery systems is imperative to enhance the efficacy of TRAIL and to elucidate the underlying cellular mechanisms. The objective of this study is to develop delivery systems that can extend the half-life of TRAIL. These delivery systems are intended for use in breast cancer treatment. In addition, the study will determine the potential of TRAIL to reach the tumor in cell culture and in vivo mouse tumor model. Materials and Methods: In this study, the TRAIL recombinant protein was purified, and drug delivery systems were developed using PLGA and exosome. The characterization of these systems was also performed. The evaluation of drug delivery systems was conducted with respect to their effectiveness on the human breast cancer cell line MDA-MB-231. The analysis of apoptotic and autophagic mechanisms was performed using flow cytometry and qPCR. The efficacy of drug delivery systems was ascertained in an in vivo mouse tumor model established in the EAC. Histopathological evaluations were performed on tissues extracted from mice employing HE staining as well as Ki-67 staining. Results: TRAIL protein loaded into PLGA and into exosome form demonstrated the capacity to suppress cell viability and to increase apoptosis in MDA-MB-231 cells. TRAIL protein in drug delivery systems increased Casp-3 and LC3B gene expressions and Annexin-V binding. In mouse models of tumor growth, the combination of PLGA formulation and exosome drug delivery system resulted in the regression of tumors and the subsequent death of tumor cells within the tissue. Conclusion: The efficiency of TRAIL protein can be enhanced through the use of PLGA and exosomal drug delivery systems. These systems have the potential to contribute to the development of biotechnological drugs for the treatment of breast cancer.