The Nanodiamond Covalently Coupled With Mitoxantrone System And It's Role With HepG2 Cell

With the pollution of the environment and unhealthy living habits,the incidence of cancer in the Chinese population has increased year by year.China as the largest developing country,the cancer incidence and mortality rate rank first in the world,seriously affecting China's development and hindering people's happy life.At present,the conventional methods of cancer therapy include chemotherapy,radiotherapy and surgical treatment,but all have certain defects,which are easy to cause long-term pain of the patients.Recently,nanotechnology is considered to be the most promising technology for the treatment of cancer,which brings new hope for the complete treatment of cancer and the relief of patients' suffering.Among the many nanomaterials,nanodiamonds(ND)are distinguished from most nanomaterials by their natural biocompatibility,high specific surface area,and the surface riched in a variety of oxygen-containing functional groups.The excellent properties of nanodiamonds stand out its application in bio-effection,especially for drug delivery.In this paper,nanodiamonds was used as drug carriers to couple anticancer drugs by covalent attachment.As a result,the ND-PEG-GLY-MTO(NPGM)nanodrug system was successfully prepared.Subsequently,it was characterized by a series of means,such as FTIR,DLS and SEM and so on.Besides,cell experiment was designed to explore its biological effects.The main work is carried out from the following aspects:(1)Nanodiamond initially is oxidized to from a range of carboxyls through the concentrated acid treatment,followed functional modification by amino-polyethylencevglycol-amino(NH2-PEG-NH2)group to enhance its water solubility.Then the introduce of glycidol(GLY)under alkaline conditions,the ND-PEG-GLY(NPG)nanocarrier was prepared by ring-opening reaction between ND-PEG and GLY.Finally,it was covalently linked with the carboxylated MTO prepare ND-PEG-GLY-MTO(NPGM) nanodrug system.(2)The MTO loaded was calculated to be 164 ± 0.94 ?g/mg from the difference between the MTO concentration before and after the absorption by analyzing the MTO solutions using a UV-Vis spectrophotometer at 613 nm.As prepared NPGM was characterized by Fourier transform infrared spectroscopy to determine that the MTO has been successfully coupled to the ND surface.Finally,the dispersive and stability experiments demonstrate that the newly synthesized NPGM nanodrug system has excellent water solubility and can be preserved for a long time.(3)It is proved that the synthesized NPG nanoparticles are non-toxic by cell morphology and cell scratching,and are an excellent drug carrier.NPGM nanomedicine has certain lethality to Hep G2 cells and has sustained release capacity,suggesting that it has good effects for cancer treatment;flow cytometry demonstrates that NPGM nanomedicine enters the cell through the co-mediated endocytic pathway in a temperature and time-dependent manner.Apart from this,apoptosis experiments demonstrate that NPGM nanodrugs do not induce apoptosis;cell cycle experiments suggest that NPGM nanodrugs may block cell division in the G1 phase,so as to the cells no longer to divide.