Abstract

Nanodiamond (ND) has the excellent biocompatibility, similarly to other sp3-carbon based materials, and is a potential drug carrier for cancer therapy. In our work, firstly, to increase the dispersity and stability of ND (size~140nm) in vitro under the physiological environment or in cell culture medium and be suitable for biomedicine applications, ND was covalently conjugated with biocompatible polymers, such as hydroxy-polyethylene glycol-4000 (PEG-4000). Secondly, doxorubicin hydrochloride (DOX), a chemotherapy drug, was physically adsorbed onto the PEGylated nanodiamond (ND-PEG-OH). These results revealed that ND-PEG-OH nanoparticle associated DOX (ND-PEG-DOX) could efficiently deliver the drug into the human liver cancer cells (HepG2) via a clathrin-dependent endocytosis pathway, and especially enhance the DOX uptake as compared to DOX alone. The uptake half-life of ND-PEG-DOX (t1/2=3.31h) was approximately two times that of free DOX uptake (t1/2=1.67h), which was related to the uptake pathway. The results from the confocal fluorescence microscopy study showed that DOX detached from ND-PEG-DOX composites inside the cytoplasm could migrate and enter the nucleolus to inhibit the cellular growth. Thirdly, in vitro dialysis determination and imaging experiments using the confocal fluorescence microscopy indicated that DOX released from ND-PEG-DOX composites had a slow and sustained drug release capability. In summary, our study has shown that ND-PEG-OH nanoparticles can act as effective drug carriers for cancer therapy.

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