PEG-conjugated single-walled carbon nanotubes enhance the cellular uptake of Coenzyme Q10: in vitro evaluation and mechanism study

Coenzyme Q10 (CoQ10) has a wide range of physiological functions and therapeutic value. However, its biomedical application as a health product or drug is limited by its insolubility and low bioavailability. Single-walled carbon nanotubes (SWCNTs) have attracted great interest for drug or therapeutic agent delivery due to their unique properties. In this study, the pristine SWCNTs are purified with different oxidizing acid, and the resulting shortened CNTs (CNTs-COOH) are conjugated with poly-(ethylene glycol) (PEG) groups. Afterwards, CoQ10 is loaded by CNTs carriers. CNTs carriers are systematically characterized and evaluated in terms of drug loading, in vitro release, cytotoxicity, and cellular uptake. The results reveal that the sizes (length) of CNTs-COOH and CNTs-PEG are 253.2 and 328.7 nm, respectively, and they have high loading capacity for CoQ10 and low cytotoxicity toward Caco-2 cells. In comparison with CNTs-COOH, CNTs-PEG exhibited better sustained-release property for CoQ10. Also, CNTs-PEG carriers loaded with CoQ10 can be effectively delivered into cells and have enhanced cellular uptake efficiency over time. Further study results of the uptake mechanism illustrate that CNTs-PEG can be internalized into cells through the broader and more efficient entry routes, including direct penetration, clathrin-mediated endocytosis and macropinocytosis pathway. In summary, the PEG-conjugated CNTs may be used as novel nanocarriers, and the findings will contribute to the rational design of multifunctional delivery vehicles for CoQ10.