Galactose Encapsulated Multifunctional Nanoparticle for HepG2 Cell Internalization

Abstract

The fluorescent dye Cy3 and galactose derivatives are covalently assembled with different ratios on the surfaces of magnetic nanoparticles (MNPs) to produce multifunctional HepG2 cancer cell–targeting agents and the effect of ligand spatial orientation on the MNP surface is investigated on targeting specificity. By using a mixture of bis‐N‐hydroxysuccinimide ester (a bifunctional linker) and OSu‐activated Cy3 (w/w = 30:1), stable and quantifiable fluorescent MNPs (Cy3@MNPs) are synthesized that could be subsequently loaded with galactosyl ligands. A mono‐antennary and two different tri‐antennary galactosyl ligands are individually immobilized on Cy3@MNPs, and the uptake efficiencies of the resulting galactosyl Cy3@MNPs by HepG2 and HeLa cells are investigated using confocal microscopy. The confocal images show that galactosyl Cy3@MNPs are sprayed over cytoplasm of the HepG2 cells, indicating that the MNP uptake occurs via receptor‐mediated endocytosis that is followed by release from endosomes. The results also reveal that the ligand spatial orientation affects the efficiency of the receptor‐mediated endocytosis and one of the tri‐antennary galactosyl ligands shows the best uptake efficiency owing to the optimal spatial presentation of the galactosyl moieties. Overall, it is shown that the MNP is a good ligand carrier and that, when pre‐assembled, the multivalent ligand structure enhances the interactions between the surface ligands of the MNPs and receptors of HepG2 cells. Additionally, the galactosyl Cy3@MNPs are not cytotoxic, indicating that they may potentially be used for in vivo applications.

Nanoscale Metal Particles as Nanocarriers in Targeted Drug Delivery System

“…In most cases, particles with diameter size less than 120 nm were reported to be well suited for localised drug delivery applications due to the fact that they can be synthesised on a large scale with high monodispersed with almost no drug loss to the malignant sites. This point has previously been made by several authors [33,34] that the localisation behaviour of Ag particles within the malignant areas is dependent on the size as their direction can be sterically hindered in cellular matrix due to the mucoadhesives of encapsulated chemotherapeutic substances [35]. The particle size of conjugate Ag particles along with their morphology does indeed give better surface chemistry effect which arises the opsonisation behaviour.…”

Recent advances in biosensing using magnetic glyconanoparticles

“…For example, Lai et al [39] synthesized HepG2 cancer cell targeting glycoMNPs incorporating a fluorescent dye (Cy3) and galactosyl derivatives of different valence (triantennary 1a, 1b and monoantennary 2a) and length (resulting in different ligand spatial presentation on the MNP surface). The ligands were attached to the aminofunctionalized MNPs by bis(N-hydroxysuccinimide) chemistry (Fig.…”

“…For instance, Lai et al [39] reported the synthesis of 10-nm MNPs functionalized with a fluorescent dye and monoantennary or triantennary galactosyl ligands to selectively target liver cancer cells (HepG2) in vitro. These galactose residues can specifically interact with the extracellular ASGP-R, which is abundantly present in HepG2 cells, thus triggering the uptake of glycoMNPs into the cell.…”

“…This procedure allowed the synthesis of glycoMNPs bearing multiple (10 5 -10 7 ) copies of the tetrasaccharide sLe X , whose interaction with selectins plays a key role in the first stages of the inflammatory cascade. The resulting glyconanoparticles were successfully used for in vivo imaging of brain lesions (for a critical discussion regarding magnetic resonance applications of the glycoMNPs described in [37][38][39], see BImaging^).…”

Improved Targeted Delivery for Chemotherapeutic Drugs

“…It seems that polyethylene glycol plays a role of increasing the residence time of MSNs in the systemic circulation, while D-Galactosamine enriches the MSNs in HepG2 cell line 3 . The antitumor drug; doxorubicin was encapsulated in the internal surface of MSNs, whereas, polyethylene glycol-galactose was grafted onto the external surface of MSNs and the loaded doxorubicin showed a pH-responsive release profile and higher cytotoxicity against the HepG2 cell line by MTT measurements, which is a highly desirable characteristic for tumortargeted drug delivery 4 .…”