The Study Of The Interactions Between Surface Enhanced Raman Nanoprobes And Cells

In recent years,nanomaterials have shown great potential in the clinical application of cancer treatment.Wide attention has been drawn and related research has gradually formed a new field of nanomedicine.The microscopic interactions in details at a subcellular level between nanoparticles and cells have been considered as one of the key issues of nanomedicine research.It is related to how to use nanoparticles for cancer treatment more effectively.The scientific question raised in this work is how the surface characteristics of nanoparticles are influenced by the cells in the process of their interaction with cells,which is an important aspect of the above mentioned research hotspot.First of all,we introduced COMSOL Multiphysics(?) to simulate the surface electric field distribution of gold nanospheres(GNPs),gold-silver core-shell nanostructures(Au@Ag)and interstitial core-shell nanostructures(Au@Gap@Ag)It shows that the electric field distribution bares a radiation pattern of a dipole antenna,and in the simulation of the gap core-shell nanostructure,we found that when the gap is 3 nm or less,the electric field is mainly distributed in the gap of the core-shell structure,yet as the gap increases,the electric field on the surface of the silver shell has an increasing tendency,and finally shows the radiation distribution of the dipole antenna,which is in line with the enhancement of the signal of the nanoprobe with internal and external standards designed next.Secondly,we designed a gold-silver core-shell nanoprobe with internal reference BDT molecules and external Raman reporter molecules of BSA and Nile blue(NB).When the internal reference BDT molecules are embedded between the gold core and the silver shell,it can effectively isolate their direct contact with the external environment.In addition,the gold-silver core-shell structure have a strong enhancement effect on the external Raman reporter molecules.After such a core-shell structure entering the cell,it can be used as a reference for external standard Raman reporter molecular signals and probe positioning through BDT signals.At the same time,by detecting the Raman spectrum of the nanoprobe and the cells after different incubation times,the change of the Raman reporter molecular signal that was physically adsorbed on surface was studied to obtain the result of the interaction between the two.At last,we combined the dark field microscopy and confocal Raman microscopy system to observe the distribution and signal changes of nanoprobes in cells at different time.In the process of uptake of the nanoprobe by the cell,we found that the nanoprobe first entered the cell through receptor-mediated endocytosis,and then was transported to the early endosome,the late endosome,and finally reached the lysosome.At the same time,we found that the nanoprobes at different time show different degrees of aggregation.Compared with the nanoprobe solution,the Raman signal of this aggregation area has been greatly enhanced,which is mainly caused by aggregation formed after the interaction of nanoprobes and cells.In brief,this research will greatly improve the understanding on the mechanism of the dynamic interactions between nanoparticles and cells at a subcellular level.More importantly,the results will provide important guidelines for the function integration and optimization of the nanoparticles,so that they can be used more effectively in clinical practice for cancer therapy.