Construction Of Multifunctional Platform Based On Nanodiamond And Its Biological Application

It is very significant to construct a multifunctional platform which integrates bio-imaging and drug delivery for the treatment of cancer.Nanodiamonds,as an important member of the carbon material family,have been widely used in biomedical field.Nanodiamonds not only have high hardness and stable chemical properties like traditional diamond,but also have good biocompatibility and low toxicity,which make it can be well applied in organisms.In addition,nanodiamonds have abundant surface groups and large specific surface area,which make it easy to graft macromolecules and other nanomaterials to form a multifunctional platform with fluorescence imaging,Raman imaging,targeted therapy,drug delivery and other functions.In this paper,the construction and biological application of multifunctional nanoplatform based on nanodiamonds are studied.The main contents are as follows:1.Preparation and biological application of nanodiamonds(NDs)conjugated upconversion nanoparticles(UCNPs)nanocomposites.Rare earth doped upconversion nanoparticles have good upconversion fluorescence,the high penetration depth in human tissues,whose excitation wavelength is in the biological window region,so they are widely used in the biomedical field.Nanodiamonds is one kind of carbon material with high drug loading rate,which has important applications in the drug delivery.Therefore,this paper proposes that connect nanodiamonds and upconversion nanoparticles to form a multifunctional nanoplatform.Firstly,carboxyl and amino groups were chemically modified on NDs and UCNPs respectively.Then,NDs and UCNPs were covalently bonded by amide reaction to form nanocomposites(UCNP-NDs).The characterization of the materials showed that UCNP-NDs had good upconversion fluorescence.The co-culture of UCNP-NDs with He La cells successfully achieved the fluorescence labeling of cancer cells by UCNP-NDs.Biotoxicity data showed that UCNP-NDs had no obvious cytotoxicity in the concentration of 0-200 μg/m L.During drug delivery of doxorubicin(Dox),UCNP-NDs exhibited high loading efficiency and p H-responsive release characteristics.Moreover,Dox-loaded UCNP-NDs showed a relatively enhanced killing effect on cancer cells compared with Dox monomer.This is because the good biocompatibility of NDs promotes the absorption of Dox in cells.The above results show that UCNP-NDs nanocomposites have many functions like upconversion fluorescence imaging and drug delivery.It provides an effective solution for precise and visual treatment in the future.2.Preparation and biological application of photosensitizer-modified nanodiamonds.Photodynamic therapy(PDT)has the advantages of minimal trauma,high selectivity and low toxicity.Chlorin e6(Ce6),which is widely studied among photosensitizers,has been widely used in cancer therapy in recent years.Nanodiamonds with strong Raman signal is a very effective Raman probe,which can be used for Raman imaging in cells.Therefore,a multifunctional nanomaterial composed of photosensitizer-modified nanodiamonds was constructed for biological research.Firstly,chitosan was coated on NDs surface to modify amino group,and then Ce6 was modified on the surface of nanodiamond by amide reaction to form nanocomposite(ND-Ce6).It was found that ND-Ce6 was about 200 nm in size and could be well dispersed in water through a series of characterization.Furthermore,we found that ND-Ce6 can produce singlet oxygen more faster than Ce6 monomer molecule through singlet oxygen probe,which is due to the fact that nanodiamonds can promote the dispersion of Ce6 in water.The data of cytotoxicity showed that ND-Ce6 had no obvious cytotoxicity in the concentration of 0-10μg/m L without laser irradiation.Under 660 nm laser irradiation,the cell killing effect of ND-Ce6 was stronger than Ce6 monomer.It indicated that ND-Ce6 could reduce the dosage of photosensitizer and side effects.Subsequently,ND-Ce6 was co-cultured with He La cells.ND-Ce6 could perform good Raman imaging in cancer cells,indicating that ND-Ce6 could label He La cells well by Raman signals.The above results show that ND-Ce6 can be used as both Raman probe and photosensitizer materials in cancer treatment,providing a solution for visualized photodynamic therapy.