YIGSR Functionalized Hybrid Exosomes Spatially Target Dasatinib to Laminin Receptors for Precision Therapy in Breast Cancer

The novel DST-FuNP@YIGSR-Exo nanoplatform combines exosome engineering with targeted drug delivery through YIGSR-mediated laminin receptor recognition. Enhanced cellular internalization and controlled release of dasatinib (DST) effectively inhibit multiple tyrosine kinases (SRC, BCR-ABL, FAK), promoting selective cancer cell apoptosis. This integrated approach demonstrates promising therapeutic potential for targeted breast cancer treatment.

Abstract

In this study, YIGSR-functionalized exosomes (Exo) are engineered and hybridized with lipid polymeric nanoparticles (LPNPs) followed by loading of chemotherapy Dasatinib (DST) to spatially target laminin receptors on tumors. Exo derived from differentiated macrophages are engineered with YIGSR targeting peptides.These YIGSR-Exo are subsequently fused with LPNPs membranes using the freeze-thaw method, resulting in fused hybrid YIGSR-Exo, which are then loaded with DST, creating DST-FuNP@YIGSR-Exo and targeted breast cancer (BC), leading to enhanced mitochondrial membrane potential (54.50 ±5.0%), increased reactive oxygen species (59.50 ± 6.0%), and apoptosis (63 ± 6.5%), ultimately inducing cell death. Further, cellular uptake and receptor blocking studies confirm the binding affinity and interaction of DST-FuNP@YIGSR-Exo with laminin receptors, Intravenous pharmacokinetic analysis of DST-FuNP@YIGSR-Exo reveals a significant improvement in AUC0-∞, with a 20.84-fold increase compared to free DST and a 1.61-fold enhancement over DST-FuNP@Exo. This is further supported by in vivo imaging and demonstrated improved tumor localization. A tumor regression study shows a 6.8-fold reduction in tumors. Tumor tissue-specific IHC for the Ki67 proliferative marker is significantly reduced in the targeted formulation. The potential of DST-FuNP@YIGSR-Exo as an effective carrier for delivering chemotherapeutic drugs, paving the path for the advancement of biologically obtained nanocarriers for targeted breast cancer.