Glycosylated Human Heavy Chain Ferritin Nanoparticles Enhance Liver-Targeted Drug Delivery

Area of Science:

• Biochemistry
• Biotechnology
• Materials Science

Background:

• Human heavy chain ferritin (FTH) is an iron-storage protein utilized in drug delivery systems.
• Glycosylation of FTH presents emerging opportunities for therapeutic applications and translational research.

Purpose of the Study:

• To biosynthesize and characterize various glycosylated FTH variants (Glc-FTH, Glcn-FTH, Gal-Glc-FTH) using enzymatic methods in E. coli.
• To evaluate the impact of glycosylation on FTH properties, including self-assembly, thermal stability, and acid sensitivity.
• To assess the potential of glycosylated FTHs in targeted drug delivery and vaccine development.

Main Methods:

• Enzymatic synthesis of glycosylated FTH variants (Glc-FTH, Glcn-FTH, Gal-Glc-FTH) in *Escherichia coli*.
• Characterization of self-assembly, thermal stability, and acid-triggered depolymerization.
• In vitro assessment of cytotoxicity, immunogenicity, apoptosis induction, half-life, and hepatic targeting capabilities.
• Evaluation of antibody induction for Glcn-FTH as a potential vaccine carrier.

Main Results:

• Glycosylation did not affect FTH self-assembly or thermal stability but significantly increased acid sensitivity for controlled depolymerization.
• Gal-Glc-FTH demonstrated low cytotoxicity, low immunogenicity, minimal apoptosis induction, prolonged half-life, and strong hepatic targeting for liver-directed drug delivery.
• Glcn-FTH also enhanced hepatic targeting but induced high-titer antibodies, suggesting suitability as a vaccine carrier.

Conclusions:

• Glycans play a crucial role in modulating FTH properties for biomedical applications.
• Engineered glycosylated FTHs offer novel strategies for developing targeted cancer drug delivery systems and vaccine carriers.
• Gal-Glc-FTH shows significant promise for hepatic targeted drug delivery due to its favorable characteristics.