Biomimetic Nanoscale Erythrocyte Delivery System for Enhancing Chemotherapy via Overcoming Biological Barriers

Overcoming multiple biological barriers, including circulation time in vivo, tumor vascular endothelium, reticuloendothelial system (RES), extracellular matrix (ECM), etc., is the key to improve the therapeutic efficacy of drug delivery systems in treating tumors. Inspired by the ability of natural erythrocytes to cross multiple barriers, in this study, a biomimetic delivery system named NE@DOX-Ang2 was developed for enhancing the chemotherapy of breast cancer, which employed nano-erythrocyte (NE) encapsulating doxorubicin (DOX) and surface modification with a targeted angiopep-2 peptide (Ang2). NE@DOX-Ang2 enhanced the capacity to cross biological barriers in a three-dimensional (3D) tumor spheroid model and in vivo in mice. Compared with a conventional drug delivery system of liposomes, the half-life of NE@DOX-Ang2 increased approximately 2.5 times. Moreover, NE@DOX-Ang2 exhibited excellent tumor-targeting ability and antitumor effects in vitro and in vivo. Briefly, the prepared nano-erythrocyte drug carrier has features of favorable biocompatibility and low immunogenicity and the advantage of prolonging the half-life of drugs, which may provide a novel perspective for development of clinically available nanomedicines.

Automated summary

The study demonstrates that a biomimetic drug delivery system named NE@DOX-Ang2 can enhance the chemotherapy of breast cancer by utilizing nano-erythrocytes encapsulating doxorubicin and surface modified with a targeted angiopep-2 peptide. This system shows strong ability to cross biological barriers, increased half-life compared to conventional liposomes, and exhibits excellent tumor-targeting and antitumor effects in vitro and in vivo.