TRAIL-PEG-Apt-PLGA nanosystem as an aptamer-targeted drug delivery system potential for triple-negative breast cancer therapy using in vivo mouse model

Abstract

Targeted drug therapy is very important for the treatment of triple-negative breast cancer (TNBC), and the development of carrier systems to deliver apoptosis-inducing proteins such as TRAIL to cells is important in cancer therapy. In this study, a nanosystem formulation (TRAIL-PEG-Apt-PLGA) encapsulating TNBC-targeted aptamer-bound-TRAIL protein was performed and the efficacy of this system was evaluated in a mouse tumor model. The characterization of TRAIL-PEG-Apt-PLGA was confirmed by FTIR, NTA and SEM microscopy. The efficacy of TRAIL-PEG-Apt-PLGA was evaluated by in vitro release assays and interactions with TNBC cells (MDA-MB-231) and healthy breast cells (MCF-10A). TRAIL-PEG-Apt-PLGA was administered intravenously to NOD/SCID gamma mouse breast tumors and evaluated in vivo. Pharmacokinetics, bioavailability testing, histological staining (DR4/DR5, TUNEL, HE staining) and molecular alterations with PCR array were evaluated in tumor tissues. TRAIL-PEG-Apt-PLGA induced apoptosis in both in vivo and in vitro studies. It was found that it regulated cellular responses along with apoptotic mechanisms in cells without developing resistance in suppressing tumor growth by making changes on Atf2, Casp8, Bcl2 and Irf5 genes and proteins. As a result, the biotechnological drug potential of TRAIL was discovered in an aptamer-bound nanosystem for the treatment of triple-negative breast cancer and innovative applications for clinical use.