Controlled delivery of hollow corn protein nanoparticles via non-toxic crosslinking: in vivo and drug loading study

In this research, controlled delivery of hollow nanoparticles from zein, the corn storage protein, to different organs of mice was achieved via crosslinking using citric acid, a non-toxic polycarboxylic acid derived from starch. Besides, crosslinking significantly enhanced water stability of nanoparticles while preserving their drug loading efficiency. Protein nanoparticles have been widely investigated as vehicles for delivery of therapeutics. However, protein nanoparticles were not stable in physiological conditions, easily cleared by mononuclear phagocyte system (MPS), and thus mainly accumulated and degraded in spleen and liver, the major MPS organs. Effective delivery to major non-MPS organs, such as kidney, was usually difficult to achieve, as well as long resident time of nanoparticles. In this research, hollow zein nanoparticles were chemically crosslinked with citric acid. Controlled delivery and prolonged accumulation of the nanoparticles in kidney, one major non-MPS organ, were achieved. The nanoparticles showed improved stability in aqueous environment at pH 7.4 without affecting the adsorption of 5-FU, a common anticancer drug. In summary, citric acid crosslinked hollow zein nanoparticles could be potential vehicles for controllable delivery of anticancer therapeutics.