Study On Nanomaterials In Tumor Marker Detection And Drug Controlled Release

At present,cancer has become one of the major diseases affecting human health.After years of research,there are many mature cancer therapeutic methods,such as radiotherapy and chemotherapy.However,these methods,while treating cancer,can also cause serious damage to normal cells.In patients with terminal malignant tumors,cancer cells begin to spread and cure is almost impossible.Therefore,early detection of cancer has become vital.The appearance of tumor markers plays an important role in the early diagnosis of cancer.There are many methods for detecting tumor markers,but poor biocompatibility and poor specificity have become major problems.Based on the above two problems,two probes were designed for the detection of tumor markers to achieve the purpose of early diagnosis of malignant tumors.On the other hand,through the drug delivery delivery system,a drug-targeted delivery model was constructed to deliver specific drug molecules to target cells and tissues,thereby achieving targeted killing of tumor cells.The specific research contents are as follows:(1)Intracellular glutathione was detected based on highly stable urchin-like gold nanoparticles.Prepared a series of urchin-like gold nanoparticle(SUL-AuNPs)probes that respond to glutathione(GSH).Three different sizes of sea urchin-shaped gold nanoparticles were prepared by changing the amount of Au seeds in the reaction system.They were modified with Rhodamine B(RB)by electrostatic interaction to obtain RB-SUL-AuNPs.After addition of GSH,the competitive reaction between GSH and RB-SUL-AuNPs covalently bound by Au-S causes RB molecules to shed from SUL-AuNPs,thereby detecting hepatocytes and cell extracts based on changes in fluorescence intensity at 575 nm,so as to achieve the purpose of early diagnosis of malignant tumors.Among them,100 nm size SUL-AuNPs have the highest sensitivity to GSH detection with the detection limit of 0.5 ?M,linear range is 2-100 ?M.At the same time,experiments have shown that SUL-AuNPs have good cell membrane permeability and good biocompatibility.(2)Monoamine oxidase B was detected by a fluorescent probe based on the ESIPT effect.Based on the fluorescence dye 2-(2'-hydroxyphenyl)-4-(3H)-quinazolinone(HPQ)with excited intramolecular proton transfer(ESIPT),a P-MAO-1 fluorescence probe that can specifically detect the activity of MAO-B,which was constructed by introducing MAO recognition group.After the reaction between probe P-MAO-1 and MAO-B,the recognition group falls off and HPQ is released,which results in proton transfer within HPQ molecule,and the conjugated structure changes,causing a change in the fluorescent signal.In the detection system,with the increase of MAO-B concentration,the fluorescence intensity of P-MAO-1 probe at 455 nm was seven times higher than that of the blank sample under the excitation of 365 nm.The optimum pH of MAO-B detected by P-MAO-1 probe was 7.4,and the optimum temperature was 37 °C.At the same time,P-MAO-1 probe had good selectivity for MAO-B detection.(3)The nucleic acid controlled release mesoporous silica nanomaterials were used as doxorubicin vectors for tumor targeting killing.We constructed the MSN@Dox@DNA drug targeted delivery model based on the drug delivery system.First,we loaded doxorubicin(Dox)into the MSN carrier and constructed the drug-loading platform MSN@Dox.Then we used DNA to encapsulate the MSN@Dox surface to construct MSN@Dox@DNA.The aptamer modified on the surface of MSN@Dox@DNA specifically recognizes cancer cells,and the primer DNA is extended by telomerase in the cell and detached from the surface of MSN@Dox,releasing Dox.Dox has a strong inhibitory effect on DNA transcriptional translation and replication,which in turn induces apoptosis in cancer cells.Although Dox is a non-specific drug,we have been able to use it to specifically kill tumor cells by modifying MSN.