H. Kim, D.Y. Lee
Keywords: gold nanoparticle, lactoferrin, oral delivery, photo thermal therapy, glioblastoma
Summary:Gold nanoparticle (AuNP) as a photothermal therapy (PTT) agent has been reported in various application due to its physical properties. If gold nanoparticle can be orally absorbed, its application may be extended. Unfortunately, it has low absorption efficiency from the gastrointestinal (GI) tract to blood stream. To overcome its limitation orally, here we newly synthesized lactoferrin (Lf, a milk protein)- polyethylene glycols (PEG)-conjugated gold nanoparticles (Lf-PEG-AuNP). This Lf-PEG-AuNP could be orally absorbed due to its interaction with lactoferrin receptor (Lf-R) on the intestinal cells. In addition, interestingly, glioblastoma in brain cancer highly express lactoferrin receptor. Furthermore, the nano-scale of gold nanoparticle could be expected to be able to pass through the Blood-Brain Barrier (BBB) due to its EPR effect because proliferation of brain cancer cells could destroy the structure of BBB. Based on these findings, we adapted nano-sized AuNP modified with the lactoferrin (Lf) and polyethylene glycols (PEG) for preparation of not only for GBM targeting efficacy but also long-circulating AuNP with improved half-life in the bloodstream. The Lf-PEG-AuNP was orally absorbed with higher bioavailability and targeted to the brain cancer cells (U87MG cells) that was orthotopic animal model. Fortunately, when specified wavelength of laser was irradiated to the head of orthotopic animals, the Lf-PEG-AuNP made the higher temperature to the head, thereby killing the brain cancer cells. Collectively this milk protein-based oral delivery of AuNP could be a promising strategy as a platform technology.