Folate-modified carboxymethyl-chitosan/polyethylenimine/bovine serum albumin based complexes for tumor site-specific drug delivery

Abstract

A ternary core/shell based nanoparticulate complex was designed for the sequential and site-specific drug delivery. First, bovine serum albumin nanoparticles (BSA NPs) were served as the core for loading gambogic acid (GA). Subsequently, the BSA NPs were adsorbed by polyethylenimine and then shielded with carboxymethyl chitosan-folate (CMCS-FA) as the outer shell for encapsulating tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), forming the GA/TRAIL co-delivery BSA (GTB) NPs. In normal tissues, the GTB NPs were negatively charged; in acidic tumor tissues, the shielding CMCS-FA was detached, allowing the release of TRAIL, which binds to the cell death receptor on the plasma membrane. The resulting positively charged complex promoted cellular internalization and escaped from lysosomes, producing a rapid release of GA, which exerted the combined tumor therapy by regulating both intrinsic and extrinsic apoptotic pathways. In vitro and in vivo studies confirmed that GTB NPs could enhance antitumor efficacy and reduce adverse effects.