TRAIL PLGA/Gelucire 48/16 and exosome carrier systems enhance anti-tumor efficacy by enabling autophagic motility

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent anticancer protein that selectively reduces the viability of malignant cells but is limited clinically by its short half-life. This study developed novel TRAIL-loaded drug carrier systems to prolong its mean residence time, consequently enhance its biological activity and enhance therapeutic efficacy in breast cancer, and evaluate tumor targeting and modulation of apoptotic and autophagic pathways in vitro and in vivo. TRAIL-loaded carrier systems were prepared using PLGA/Gelucire 48/16 nanoparticles and exosome-based formulations. Following physicochemical characterization, biological effects were assessed in MDA-MB-231 cells and an EAC mouse tumor model, with apoptotic and autophagic responses analyzed by flow cytometry and qPCR. Histopathological assessments included HE staining, TUNEL assay, and Ki-67 IHC. Both PLGA/Gelucire 48/16 nanoparticles and exosome-encapsulated TRAIL significantly suppressed cell viability and enhanced apoptosis in MDA-MB-231 cells. Treatment with these carrier systems upregulated the expression of Caspase-3 and LC3B genes in-vitro and in mouse tumor tissues, indicating activation of apoptotic and autophagic pathways. In the EAC tumor model, TRAIL-loaded formulations reduced tumor growth, decreased the Ki-67 proliferation index, and induced marked tumor regression. Encapsulation of TRAIL in PLGA/Gelucire 48/16 or exosome-based carriers enhances its stability and antitumor activity, highlighting the potential of these carrier platforms to improve TRAIL-encapsulated biotechnological therapeutics for breast cancer treatment.