| Malignant tumor has been severely threatening human health.Nasopharyngeal carcinoma is one of common malignant tumors.The incidence of nasopharyngeal carcinoma is particularly high in Guangdong province.Due to good targeting,high relaxation rate and high photothermal conversion efficiency,new biomedical magneto-optical nanoprobes take an important part in biological imaging and photothermal therapy of tumors.Ferric oxide materials are employed as contrast agents for magnetic resonance imaging(MRI)while gold nanomaterials are used for photothermal therapy.Multi-functional nanoprobes can integrate diagnosis and treatment of tumors,enabling tumor imaging in high relaxation rate and therapy safely at the same time.The imaging and photothermal therapy functions of multi-functional nanoprobes have already been studied deeply by numerous experiments which are focused mainly on design,preparation,characterization and toxicity analysis.The magnetism of nanoprobes can directly impact the relaxation rate of MRI.Moreover,nanoprobes interact with biological tissues in vivo.However,the mechanism underlying magnetism enhancement of new magneto-optical nanoprobes in addition to the interaction between nanoprobes and lipid membrane or membrane protein can barely be comprehended by experiments without the imformation on atomic or molecular level.Multi-scale pilot calculation is significant for understanding the mechanism underlying.Design of magneto-optical nanoprobes requires improvement.The optimal rare-earth doping amount,and the mechanism underlying diagnosis and treatment through probe-tumor interaction,are yet to be clarified for lack of theoretical study.It is worth carrying out the computational study of the mechanism underlying magnetism enhancement of magneto-optical nanoprobes as well as the impact of nanoprobes on membrane protein.Applying simulation methods on multiple scale including the first-principle calculation and molecular dynamics calculation,this paper focuses on the mechanism underlying magnetism enhancement of magneto-optical nanoprobes and the impact of nanoprobes on latent membrane protein,which is key to nasopharyngeal carcinoma.Based on the SDFT+U(spin-polarized density functional theory)method of first-principle calculation,the magnetism enhancement due to rare-earth ion Dy3+doping to ?-Fe2O3 is studied in this paper.Quantum Espresso software is employed for pilot calculation.The calculation results indicate that the total magnetic moments of the system climb up and then decline with the increase of Dy3+doping amount.The excessive doping amount brings about lattice distortion and non-collinear magnetic moments,leading to the decline of the total magnetic moments.This work predicts the existence of optimal Dy3+doping amount and reveals the mechanism underlying magnetism enhancement of nanoprobes through computational study.Based on the pilot calculation,our group conducted experiments about ?-Fe2O3 nanoparticles doped with Dy3+The experiment results indicate that the saturation magnetization of y-Fe2O3 nanoparticles climb up and then decline with the increase of Dy3+doping amount,similar to the results of first-principle calculation.In our experiments,the transverse relaxivity of ?-Fe2O3 with optimal Dy3+doping amount nearly doubles that of ?-Fe2O3 without doping.The spin-spin relaxation of Dy3+-doped ?-Fe2O3 is related to saturation magnetization with a powerlaw relationship(r2?Ms1.3902).Through the guidance of first-principle calculation,this paper succeeds in the preparation of y-Fe2O3 nanoparticles with high relaxivity.The safe MRI contrast agents with high relaxivity are obtained in this paper,establishing the foundation of application of magneto-optical nanoprobes on imaging and diagnosis of tumors.In this paper,the interaction between gold nanoprobes and lipid membrane,and the impact of nanoprobes on latent membrane protein 1(LMP1),are explored by Gromacs software.LMP1 is a key protein to nasopharyngeal carcinoma.The annealing simulation is successfully employed to absorb PEG3-SH ligands towards the surface of the gold nanoprobe with high coverage ratio.Then interaction between the PEGylated gold nanoprobe and a DPPC(1,2-DIHEXADECANOYL-RAC-GLYCERO-3-PHOSP)lipid bilayer is studied.The calculation results indicate that the hydrophobic space of lipid bilayer comes into being spontaneously.Moreover,the nanoprobe and the lipid bilayer will attract and approach each other,revealing the mechanism underlying interaction.Besides,the impact of the PEGylated gold nanoprobe on LMP1 is explored in this paper.The simulation results presents attraction between the nanoprobe and the protein.The secondary structures of LMP1-TRAF3 are affected by the nanoprobe.Owing to anisotropy of rod-like gold nanoprobes,the localized surface plasmon resonance(LSPR)along the longitudinal axis is more significant than its transversal counterpart.The protein coinciding with longitudinal axis seem to be more unstable than those coinciding with the transversal axis.The heating-up nanoprobe will increase the instability of LMP1,particularly residue Asp 210(Aspartate).The molecular dynamics calculation of a whole protein cannot lead to a deep undertanding of the mechanism underlying on atomic level,so the first-principle calculation is employed to figure out the impact of gold surfaces on the key residue Asp 210.The longitudinal and the transversal axes of gold nanoprobes are represented by gold surface Au(111)and Au(110),respectively.The results of first-principle calculation illustrates that Au(111)has a more significant impact on the protein than Au(110),meaning that the longitudinal axis of nanoprobes has a more significant impact than the transversal axis.To an extent,the first-principle calculation corresponds to the molecular dynamics calculation.By calculation on multiple scale,this paper reveals the mechanism underlying impact of magneto-optical nanoprobes on the key protein of nasopharyngeal carcinoma,providing theoretical guidance to the application of nanoprobes on photothermal therapy of tumors.In summary,this paper reveals the mechanism underlying magnetism enhancement in magneto-optical nanoprobes and the impact of nanoprobes on latent membrane protein,which provides theoretical guidance to the application of magneto-optical nanoprobes on high relaxation rate imaging and photothermal therapy of tumors.This paper remarkably establishes the theoretical basis for diagnosis-treatment integration of tumor by nanoprobes. |
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