Covalent linkage of nanodiamond-paclitaxel for drug delivery and cancer therapy

Abstract

A nanoparticle-conjugated cancer drug provides a novel strategy for cancer therapy. In thisstudy, we manipulated nanodiamond (ND), a carbon nanomaterial, to covalentlylink paclitaxel for cancer drug delivery and therapy. Paclitaxel was bound tothe surface of 3–5 nm sized ND through a succession of chemical modifications.The ND-paclitaxel conjugation was measured by atomic force microscopeand nuclear magnetic resonance spectroscopy, and confirmed with infraredspectroscopy by the detection of deuterated paclitaxel. Treatment with 0.1–50 µg ml − 1 ND-paclitaxel for 48 h significantly reduced the cell viability in the A549 human lungcarcinoma cells. ND-paclitaxel induced both mitotic arrest and apoptosis in A549 cells.However, ND alone or denatured ND-paclitaxel (after treatment with strong alkalinesolution, 1 M NaOH) did not induce the damage effects on A549 cells. ND-paclitaxel wastaken into lung cancer cells in a concentration-dependent manner using flow cytometeranalysis. The ND-paclitaxel particles were located in the microtubules and cytoplasm ofA549 cells observed by confocal microscopy. Furthermore, ND-paclitaxel markedlyblocked the tumor growth and formation of lung cancer cells in xenograft SCIDmice. Together, we provide a functional covalent conjugation of ND-paclitaxel,which can be delivered into lung carcinoma cells and preserves the anticanceractivities on the induction of mitotic blockage, apoptosis and anti-tumorigenesis.