Surface-enhanced Raman Spectroscopy Detection And Synergistic Therapy For Cancer Cells

As the most basic structure and functional unit of an organism,cell is a dynamic and complex biological system and keeps the constant and rapid exchange of matter and energy with the environment.Therefore,there is a significance difference at temporal and spatial level in cell activities.Moreover,the dynamic changes of the genetic information in cells are closely related to the occurrence and development of disease,and intercellular signal is the basis of achieving a variety of biological functions and life activities(e.g.,cell apoptosis,proliferation and differentiation,the vitiation of cell component or its micro environmental).Therefore,the accurate study of the information and function of intracellular substances has always been the most fundamental and important in biomedical research,especially in the diagnosis and treatment of cancer.As a very aggressive disease,cancer is not only involved in many processes,such as cell growth and division,but also has a high morbidity and mortality.The therapy efficiency of conventional chemotherapy is often reduced because of the nonspecific distribution of many anticancer drugs and the rapid removal by cancer cells due to the generation of drug resistance.Compared with the limited curative effect and the possible side effects of single chemotherapy method,it is possible to achieve the cancer targeted therapy if combine conventional chemotherapy with nanotechnology.And can further produce more efficient therapy under low dose of anticancer drugs,avoiding the side effects of large dose.This paper aimed at understanding the molecular mechanisms of disease and put forward the solution in the treatment drug resistance and side effects of the problems existed in the process of drug treatment and the cancer cell were regarded as the research target.Our study including two parts: selectively studied the nuclear genetic information of cancer cells;providing a new synergistic treatment method of cancer reduce the possibility of drug resistance and achieve targeted therapy for cancer cells.The main content is as follows:First,we choose a small Raman signal molecule EDU with an alkynyl group as an internal standard to achieve the accurate detection of the cell nuclei information.The molecule has two characteristics: one is that the ability of targeting to nucleus and the other is Raman spectra were located at the silent rejoin of the cell.After incubated with cell,the molecule can locate in the nucleus and their location was identified using confocal fluorescence microscope.Next,the nuclear targeted nanoprobes were obtained by modifying polyethylene glycol(PEG)and nucleus targeting peptide on the surface of gold nanorods.And the nanoprobes can signicantly enhanced the Raman signal of EDU and cell nucleus.After then,dark-field/fluorescence microscopy and super resolution fluorescence microscopy were employed to locate the distribution of the nanoprobes in cells.Our results indicate that the nanoprobe locating and in situ accurate SERS detection of cell nucleus can be synchronously completed.Spectral information pointing to the components of cell nuclei can be selectively analyzed.Nanoenzyme combined chemotherapy for synergistic targeted cancer therapy.Step 1: targeted therapy.First,nanoenzyme with specific targeting property was prepared by modifying the RGD(cancer cell-targeted peptides)on the surface of gold nanoparticles.Then,the glucose oxidase with catalytic function was further assembly on the RGD modified gold nanoparticles to obtain the nanoenzyme with the ability to target and catalysis function.Based on the catalysis function of nanoenzyme,the glucose of the cells was consumed and amount of hydrogen peroxide was produced to damage cancer cells.The second step is chemotherapy with low drug concentration.After the treatment of nanoenzyme,the cells were damaged to a certain extent,and we further treated the cells with chemotherapy.And we found that only a low dose of drugs can induce the cell death.Last but not the least,the synergistic therapy of low-dose chemotherapy combined with nanoenzyme was compared with the treatment effect of individual chemotherapy drugs,and the possible therapeutic mechanism of the treatment was also analyzed.Our results indicate that the combined therapeutic effect produced by AuNP-PEG-RGD-GOx and DOx is greater than the sum of the individual therapeutic effect of AuNP-PEG-RGD and DOx alone,which means AuNP-PEG-RGD-GOx and DOx can synergistically induce cancer cell apoptosis.Our proposed strategy not only can ensure effectively cause cancer cell apoptosis but also significantly reduce the side effect on the normal cells compared with cells treated with free anticancer drug.