Engineering E2 Bionanoparticles for Targeted Delivery of Chemotherapeutics to Breast Cancer Cells

Naturally occurring protein nanocages are promising drug carriers as both the interior and exterior can be decorated for drug encapsulation and cell targeting. To provide surface functionalization, we added a SpyTag to E2 nanocages (ST-E2) to enable tunable decoration using the robust SpyCatcher bioconjugation strategy. Additionally, the E2 core was mutated with four phenylalanine substitutions for doxorubicin loading and pH-responsive release. By decorating the exterior with a highly cell-specific epidermal growth factor receptor (EGFR)-targeting protein conjugate, 4GE11-mCherry-SpyCatcher, we demonstrated targeted cell death in inflammatory breast cancer cells compared to healthy breast epithelial cells at concentrations below the IC50 of free doxorubicin.