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

Abstract

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.

Current perspectives and trends in nanoparticle drug delivery systems in breast cancer: bibliometric analysis and review

“… Alimoradi et al (2018 ) developed a stable nitric oxide (NO)-releasing nanoparticle (polystyrene-maleic acid [SMA]-tert-dodecane S-nitrosothiol [tDodSNO]) to enhance the anticancer properties of doxorubicin (Dox) and overcome the biologic barriers of in vitro and in vivo studies. As delivery systems and nanomedicine platforms, the dual-functionalized graphene oxide (GO)-based nanocarrier, the Salmonella enterica serovar Typhimurium, multifunctional hybrid NPs, PEG-PLGA NPs coated with hyaluronic acid, and biomimetic nanoscale erythrocyte could overcome biological barriers to enhance tumour responses to chemotherapy in BC treatment ( Suh et al, 2019 ; Cristofolini et al, 2020 ; Almoustafa et al, 2021 ; Liu et al, 2021b ; Zhang et al, 2021b ).…”

Red blood cells: a potential delivery system

“…From confocal microscopy, we can demonstrated that the loaded drugs can extravasate via the tumor vessel and penetrate deeply into the tumor [74]. Simple methods, like shear force, can get nanoscale vesicles [41,79,80]. The nano RDVs have intact membrane proteins and glycolipids, exhibiting better stability than single liposomes.…”

Erythrocyte‐Inspired Functional Materials for Biomedical Applications

“…[ 1,153 ] The EM‐NVs have been utilized to directly encapsulate chemotherapy drugs, enzymes, proteins, polysaccharides, toxins, and genetic material. [ 154–157 ] The camouflaged synthetic NPs included polymer NPs (e.g., PLGA, liposomes), [ 156,158 ] metal NPs (e.g., gold, Fe 3 O 4 , hollow copper sulfide), [ 41,159 ] inorganic non‐metal NPs (e.g., mesoporous SiO 2 ), [ 160 ] albumin NPs (e.g., BSA), and nanogels. [ 30,161 ] It is noteworthy that there are little target ligands on the EM‐NVs to provide the navigation for cargoes to locate at the disease region.…”