Carbon Nanotube (CNT) is an extremely important and well-known nanomaterial widely used in drug delivery.Although it is largely non-toxic, prolonged exposure at higher concentrations could lead to inflammation, generation of oxidative stress, cytotoxicity, and genotoxicity.This article explores the factors contributing to CNT toxicity and discusses preventive measures.
Overview of CNTs:
CNTs are cylindrical nanostructures composed of carbon atoms, discovered by Sumio Iijima in 1991.
Two main types: Single-Wall Carbon Nanotubes (SWCNTs) and Multi-Wall Carbon Nanotubes (MWCNTs).
SWCNTs consist of a single graphite layer; MWCNTs have multiple concentric graphite layers.
Properties and Applications:
CNTs have exceptional tensile strength, biocompatibility, and electrical and thermal properties.
Applications include medicine (e.g., targeted drug delivery), nanosensors, hydrogen storage, and field emission devices.
Routes of Exposure:
CNTs can be introduced to the human body via oral, inhalation, intravenous (IV) injection, transdermal, intraperitoneal, and subcutaneous routes.
CNTs are distributed throughout the body and may remain, translocate, or be excreted.
Toxicological Effects:
Pure CNT exposure reduces cell proliferation, induces apoptosis, cell cycle arrest, and necrosis by interacting with proteins and altering their structure.
CNTs cause oxidative stress, leading to inflammation and cytotoxicity through the release of cytokines regulated by nuclear factor-Kappa B and protein kinases.
Increased reactive oxygen species (ROS) levels cause protein, lipid, and DNA damage.
Organ-Specific Effects:
CNTs accumulate in organs like the spleen, kidneys, lungs, and liver, inducing inflammation, cell proliferation, and elevated enzyme production, leading to toxicity (e.g., hepatotoxicity).
Factors Affecting CNT Toxicity:
Purity: Metal impurities (e.g., iron, nickel) in CNTs can increase toxicity through oxidative stress; purification methods like ultra-sonication help reduce this.
Shape: Rod-shaped nanomaterials and those with larger aspect ratios are generally more toxic than spherical ones.
Size: Larger CNTs cause "frustrated" phagocytosis, preventing complete removal and leading to inflammation; smaller CNTs show reduced toxicity.
Functionalization: Modifying CNTs (e.g., coating with PEG) reduces toxicity and improves biocompatibility and dispersibility.
Mitigation Strategies:
Functionalizing CNTs (e.g., with PEG) improves pharmacokinetics, reduces toxicity, and enhances excretion through urine and feces.
Chemical modifications and size adjustments of CNTs can further mitigate toxicity.
Curcumin-coated, lysine-functionalized MWCNTs reduce ROS production, inflammation, and promote recovery of mitochondrial function.