Dual-Targeting Exosomes for Improved Drug Delivery in Breast Cancer
Nam HB Tran, Diem D. N. Nguyen, Ngoc Mai Nguyen, Chau Tran, Ngoc Thanh Nguyen Thi, Duyen T. K. Ho, Hoai‐Nghia Nguyen, Lan N. Tu
Abstract
Aims: The authors investigated whether displaying more than one homing peptide enhanced the tumor-targeting efficiency of exosomes. Materials & methods: Exosomes from human embryonic kidney cells (HEK293F) were engineered to display either mono- or dual-tumor-penetrating peptides, iRGD and tLyp1. Exosomes were purified via tangential flow filtration followed by ultracentrifugation. Results: When loaded with doxorubicin (Dox), the dual iRGD-tLyp1 exosomes strongly enhanced Dox uptake in both MCF-7 and MDA-MB-231 breast cancer cell lines, superior to single iRGD or tLyp1 exosomes. The dual iRGD-tLyp1 exosomal Dox was also the most potent, with IC50/GI50 values being 3.7–17.0-times lower than those of free Dox and other exosomal Dox. Conclusion: Selecting appropriate combinatorial homing peptides could be an approach for future precision nanomedicine.