Inside-out extracellular vesicles-like biomimetic magnetic nanoparticles for efficient screening P-Glycoprotein inhibitors to overcome cancer multidrug resistance

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 222; p. 113134
• Main Authors: Zhang, Xiaolin, Jia, Lanlan, Liu, Nanxin, Zhao, Ying, Zhang, Tingting, Xie, Xiaoyu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2023
• Subjects: Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; Biological Products - pharmacology; Biomimetics; Cell membrane biomimetic platform; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Early Detection of Cancer; Humans; Inside-out extracellular vesicles; Magnetite Nanoparticles; Multidrug resistance; Neoplasms - drug therapy; P-Glycoprotein inhibitors; Cell membrane biomimetic platform; P-Glycoprotein inhibitors; Inside-out extracellular vesicles; Multidrug resistance
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2023.113134

The discovery of P-Glycoprotein (P-gp) inhibitors to block chemotherapy drugs efflux is considered an attractive treatment strategy for overcoming cancer multidrug resistance (MDR). Cell membrane biomimetic platform has emerged as a promising candidate method for screening small molecule P-gp inhibitors from natural products. However, randomly oriented cell membrane coating does not guarantee the inward-opening conformation of P-gp, limiting the precise screening of P-gp inhibitors. Herein, inside-out orientation extracellular vesicles camouflaged magnetic nanoparticles (IOVMNPs) were prepared to discover P-gp inhibitors with low toxicity and high efficiency from natural products. The orientation of extracellular vesicles on the surface of IOVMNPs was rigorously confirmed by immunogold electron microscopy and sialic acid quantification assay. Finally, two potential P-gp inhibitors, honokiol and magnolol, were captured by obtained IOVMNPs. The effect of MDR reversal in combination with chemotherapy drugs was further verified by pharmacological activity experiments. The inside-out orientation extracellular vesicles encapsulation strategy provides an effective tool for the discovery of novel P-gp inhibitors from nature products, thus further extending the application field of orientation assembly cell membrane biomimetic magnetic nanoparticles. This inside-out extracellular vesicles coating also proposes a new concept for the assembly of cell membrane biomimetic platform. [Display omitted] •Inside-out orientation extracellular vesicles coated magnetic nanoparticles (IOVMNPs) were developed.•IOVMNPs showed satisfactory orientation and adsorption properties.•IOVMNPs were applied to efficient screen P-Glycoprotein inhibitors.•Two active compounds combined with DOX showed better anti multidrug resistance effect.