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

Millicent O Sullivan; Wilfred Chen

doi:10.1007/978-1-0716-3469-1_13

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

Methods Mol Biol. 2024:2720:177-189. doi: 10.1007/978-1-0716-3469-1_13.

Authors

Millicent O Sullivan¹, Wilfred Chen²

Affiliations

¹ Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA. [email protected].
² Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA. [email protected].

PMID: 37775666
DOI: 10.1007/978-1-0716-3469-1_13

Abstract

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.

Keywords: DOX; EGFR; SpyCatcher.