Milk protein-shelled gold nanoparticles with gastrointestinally active absorption for aurotherapy to brain tumor

Hyung Shik Kim; Seung Jae Lee; Dong Yun Lee

doi:10.1016/j.bioactmat.2021.06.026

Milk protein-shelled gold nanoparticles with gastrointestinally active absorption for aurotherapy to brain tumor

Bioact Mater. 2021 Jun 28:8:35-48. doi: 10.1016/j.bioactmat.2021.06.026. eCollection 2022 Feb.

Authors

Hyung Shik Kim¹, Seung Jae Lee¹, Dong Yun Lee^{1

2}

Affiliations

¹ Department of Bioengineering, College of Engineering, and BK FOUR Biopharmaceutical Innovation Leader for Education and Research Group, Hanyang University, Seoul, 04763, Republic of Korea.
² Institute of Nano Science and Technology, Hanyang University, Seoul, 04763, Republic of Korea.

Abstract

Orally absorbable gold nanoparticles (AuNP) having cancer ablation therapy is strongly demanded to treat glioblastoma multiforme (GBM) for patients with its highest incidence rate. Here, we develop a milk protein lactoferrin-conjugated AuNP for its oral absorption and targeting to the GBM through the interaction between lactoferrin (Lf) and lactoferrin receptor (LfR) that is highly expressed in the intestine, blood-brain barrier and GBM. For stability and long circulation of AuNP, glutathione and polyethylene glycol (PEG) is introduced, which is called to Lf-PEG-AuNP. When Lf-PEG-AuNP are orally administered to orthotopic GBM-bearing mice, 11-fold and 8-fold higher concentrations of AuNP are measured in bloodstreams and GBM in the brain, respectively, compared with unconjugated-AuNP. Therefore, orally administered Lf-PEG-AuNP exhibit an outstanding temperature rise in GBM by irradiating laser and significantly reduce tumor volume. Collectively, we suggest that the Lf-PEG-AuNP can fundamentally target GBM in the brain through oral absorption, and that its efficient photothermal therapy is possible.