Scheme 1.

(1) The A549/T cells were suspended in hypotonic lysis buffer supplemented with protease inhibitor cocktail followed by homogenization, series of centrifugation, and sonication to produce A549/T cell membrane vesicles. (2) The cationic bovine serum albumin (CBSA) was synthesized from native bovine serum albumin (BSA) by ethylenediamine modification reaction, and CBSA hybrid nanoparticles (CBSA-HNPs) were prepared by conservation method. (3) A549/T cell membrane-coated hybrid nanoparticles (A549/T CM-HNPs) were prepared by co-incubating cell membrane vesicles and hybrid nanoparticle core, followed by sonication and co-extrusion through a 200 nm polycarbonate membrane. (4) A549/T CM-HNPs targeted homologous A549/T cells via homotypic-binding mechanism, releasing (5) paclitaxel (PTX) and disulfiram (DSF) into the cytosol. (6) The multidrug resistance (MDR) modulator DSF inhibited the ATP concentration, downregulated the MDR-1 gene, and therefore suppressed P-glycoprotein (P-gp) and increased intracellular PTX concentration, thus inducing (7) caspase-3-dependent MDR tumor cell (A549/T) apoptosis.