Protonated nanoparticle surface governing ligand tethering and cellular targeting.
Nanoparticles have shown tremendous potential for effective drug delivery due to their tiny size and cell membrane penetration capabilities. Cellular targeting with nanoparticles is often achieved by surface modifications followed by ligand conjugation. However, the efficiency of the nanoparticles reaching the target cells and getting internalized depends on the stability of targeting ligands and the chemical nature of the ligand nanoparticle binding. Recent advancements in nanobiomaterials research have proven the superoxide dismutase (SOD) mimetic activity of cerium oxide nanoparticles (CNPs) in protecting cells against oxidative stress. Due to their excellent biocompatibility, CNPs can be used as a potential drug carrier that can transport and release drugs to the malignant sites. Here we combine single molecule force spectroscopy (SMFS) and density functional theory (DFT) simulations to understand the interaction between transferrin, a ligand protein overexpressed in cancer cells, and CNPs. SMFS studies demonstrate an increase in the transferrin adhesion to the nanoparticles' surface with an increase in positive zeta potential of CNPs. Binding energy values obtained from DFT calculations predict an increase in bond strength between the transferrin and CNPs upon surface protonation and charge modification. Transferrin-conjugated CNPs were tested for their binding stability and preferential cellular uptake efficiency by incubating them with human lung cancer cells (A549) and normal embryo lung cells (WI-38). The results demonstrate the importance of tuning the surface properties of nanoparticles for better ligand adsorption and cellular uptake.
Advanced Materials Processing and Analysis Center, Department of Mechanical, Materials and Aerospace Engineering, University of Central Florida, Orlando, Florida 32816, USA.
Abhilash
A
Vincent
Suresh
S
Babu
Eric
E
Heckert
Janet
J
Dowding
Suzanne M
SM
Hirst
Talgat M
TM
Inerbaev
William T
WT
Self
Christopher M
CM
Reilly
Artëm E
AE
Masunov
Talat S
TS
Rahman
Sudipta
S
Seal
D002563:Cerium / Q000737:chemistry*; D003460:Crystallization / Q000379:methods*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D008024:Ligands; D046911:Macromolecular Substances / Q000737:chemistry; D008968:Molecular Conformation; D049329:Nanostructures / Q000737:chemistry* / Q000627:therapeutic use / Q000648:ultrastructure*; D036103:Nanotechnology / Q000379:methods*; D010316:Particle Size; D011522:Protons; D013499:Surface Properties
D004337:Drug Carriers; D008024:Ligands; D046911:Macromolecular Substances; D011522:Protons; D002563:Cerium; C030583:ceric oxide