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

Autor: Seung Jae Lee, Hyung Shik Kim, Dong Yun Lee
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Bioactive Materials, Vol 8, Iss, Pp 35-48 (2022)
Bioactive Materials
Popis: 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.
Graphical abstract Graphical abstract text: Lf-PEG-AuNP has strong absorption capacity at the GI tract and efficient accumulation on the GBM due to LfR-mediated transport. Therefore, external 532 nm NIR laser irradiation on the specific GBM region, resulted about 60 °C heat generation. The successful PTT treatment of Lf-PEG-AuNP, decreased GBM volume by 80% and the apoptosis and necrosis were observed at the treated site.Image 1
Highlights • Glioblastoma multiforme is notoriously malignant, especially in the elderly. • Oral formulation of therapeutic drugs reduce stress during administration. • Milk protein Lactoferrin (Lf) enables oral absorption and GBM targeting of drug. • Lf receptor-mediated transportation of Lf-shelled gold nanoparticle was verified. • Photothermal therapy of gold nanoparticle targeting GBM confers therapeutic effect.
Databáze: OpenAIRE