Surface Coating Highly Improves Cytocompatibility of Halloysite Nanotubes: A Metabolic and Ultrastructural Study

Halloysite clay nanotubes (HNTs) are natural materials with a characteristic hollow tubular structure in the nanometer range. Owing to this feature, they were found to be a suitable nanosized container for the loading of biologically active molecules like biocides and drugs. Also, HNTs have been reported to be of potential interest for other biological applications, such as gene delivery carriers, ultrasound contrast agents, cancer therapy, and stem cells isolation. Therefore, biocompatibility of halloysite represents one the main requisites for the employment of HNTs for clinical purposes. Here we present a study aimed at assessing HNTs biocompatibility before and after their surface coating with poly(ethylene glycol) (PEG), a polymer which has been reported to increase biocompatibility, to prolong circulation time, and to prevent protein adsorption and aggregation in biological environments. The dose- and time-dependent cytotoxicity of noncoated and PEG-coated HNTs obtained was evaluated in vitro by MTT cell viability assay carried out on both HeLa and HepG2 cells, two different human cancer cell lines. Binding and uptake of nanotubes were also analyzed at ultrastructural level by transmission electron microscopy. Interestingly, the results obtained showed that both the HNTs tested were actively taken up by the cells but, while noncoated nanotubes exhibited significant concentration- and time-dependent toxicity, PEG-coated HNTs were found to be highly biocompatible, being then suitable candidates for biomedical applications.