Folic acid-modified soy protein nanoparticles for enhanced targeting and inhibitory

Soy protein isolate (SPI) was hydrolyzed by compound enzymes to give water soluble low molecular soy protein (SP). SP and folic acid (FA) modified SP was polymerized with N-3- acrylamidophenylboronic acid (APBA) monomer in aqueous solution to give SP nanoparticles (SP NPs) and FA modified nanoparticles (FA-SP NPs), respectively. These NPs display excellent stability in different conditions, and have a uniform spherical shape with a diameter around of 200   nm. Doxorubicin (DOX) was then successfully loaded into SP and FA-SP NPs with a desirable loading content of 13.33% and 16.01%, respectively. The cellular uptake and cytotoxicity of DOX-loaded SP NPs and FA-SP NPs were investigated using the two-dimensional (2D) monolayer cell model and three-dimensional (3D) multicellular spheroids (MCs). In vivo, tumor accumulation and growth inhibitory were then examined using H22 tumor-bearing mice. All these results demonstrated that conjugation of FA can efficiently enhance SP-based NPs' tumor accumulation and antitumor effect.