Disintegration, functionalization and drug-delivery application of nanodiamond

Abstract

In recent years, with the rapid development of nanomedicine, the nanomaterials for bio-medical applications have received much attention. Although there are a variety of nanomaterials such as lipid, carbon nanotube, etc. that have been studied as drug carrier, they are restricted by the potential toxicity and high cost of production. So, it is necessary to find a good alternative for the future drug delivery applications. Detonation nanodiamond, as an important carbon nanomaterial, possesses many excellent properties such as facile functionalization, large specific surface area, low toxicity and high chemical stability and so on, which make them advantageous in bio-medical applications over many other nanomaterials. In this work, the carboxyl functionalized and well-dispersed nanodiamond (ND-COOH) is obtained through disintegration and chemical modification, and then the functionalized nanodiamond is characterized by transmission electron microscope, X-ray diffraction, Fourier transform infrared spectroscopy, etc. to analyze its morphology and structure and the toxicity. Besides, the drug loading and release properties are also examined. The ND-COOH exhibits high zeta potential in aqueous solution, which enables them adsorb doxorubicin (dox) molecules onto the surface through electrostatic interaction, and the maximal loading reaches to 325 μg/mg, which is higher than most of reported results. It is because the bond between dox and ND-COOH origins from the electrostatic attraction between negatively charged-COO- on the ND and positively charged–NH3 in the dox. So, when the drug compounds are dispersed into low pH environment, the high H+ concentration would promote the transformation of –COO- into –COOH, which would weaken the electrostatic attraction between ND and dox and hence accelerate the drug release. This leads a drug release to reach 85% in pH 5.0 PBS and less than 40% in pH 7.4 PBS, exhibiting interesting pH-responsive drug release behavior. Finally, the toxicity and in vitro cancer cell killing results of ND-COOH and ND-dox preliminarily show that in the concentration range from 0 to 150 μg/mL, the functionalized ND-COOH does not inhibit the viability of SGC-7901 cells, exhibiting low toxicity. In contrast, the ND-dox shows obvious cytotoxicity towards SGC-7901 cells by strongly inhibiting their viability to lower than 40% in 150 μg/mL group. This work details and systematically discusses the disintegration, functionalization, drug loading and release properties of ND, which would be significant in promoting the biomedical application of ND.