Detection And Therapy Of Tumor By Nanoparticle Nucleic Acid Probe System

With the increasing proportion of people suffering from cancer in now society,the diagnosis and treatment of cancer has become an important research focus.Advanced cancer is difficult to treat and expensive at present,and early detection and targeted elimination of small amounts of early cancer is one of the best ways to solve the cancer problem.Accurate targeting of tumor cells,ultra-sensitive and specific detection of tumor marker factors,fluorescence imaging and treatment of tumor cells can effectively find early tumors,locate and remove them,which means precision medicine has great scientific research potential and broad clinical application prospects.Nanomachines for precision medicine use nano-sized particles of various materials to combine functional molecular groups with specially designed DNA sequence structure,which can be designed and programmed to perform some specific reaction actions by virtue of their complementary hybridization characteristics and expansibility,and are the basis of the diagnosis and treatment platform.Nanomachine diagnosis and treatment platform can flexibly design a variety of functions and characteristics and small trace side effects,using this basic platform and optimize the design of some specific performance to achieve more efficient and excellent precision diagnosis and treatment.Although nanomachines are micro dose and have little damage to normal tissues and organs cells,precise targeting and enrichment of tumors has always been the focus of research and optimization.The detection of tumor marker factors such as mirnas by nanomachines can have higher detection limits with clever design,signal amplification design to produce more accurate fluorescence imaging localization and measurement.Abnormal expression of miRNA in tumor cells promotes abnormal physiological activities of cells,while nanomachines,in combination with miRNA collection,will affect the level of miRNA in cells and regulate the functional activity of cells.In view of the above three optimizable directions,we designed three nanomachines for tumor diagnosis and treatment,the main contents are as follows:1.Homologous cell membranes were used to optimize targeting and cell uptake.It was studied that different tumor cells McF-7,A549,Hela and mixed membrane-wrapped nanomachines could promote more enrichment and uptake with homologous tumor cells,greatly improving the cell uptake rate of nanomachines.It reduces the damage of uningested free nanomachines to normal organisms.The excellent cell uptake rate enhanced by mixed cell membrane encapsulation improves detection and treatment effectiveness,making it an excellent nanomedicine strategy that can be combined with other strategies.2.The optimized design of nanomachine DNA structure can multiply amplify signals,that is,when the detection system and the target miRNA-155 catalytic card are installed autonomously,miRNA-155 and the secondary catalytic chain are released simultaneously.When miRNA-155 is cyclically amplified,the secondary catalytic chain also circulates and amplifies signals in another set of catalytic card autonomous loading system,even more than third catalytic chain.The ultra-sensitive detection of miRNA-155,one of the trace tumor markers,and multiple exponential amplification of fluorescence signal can achieve the purpose of diagnostic imaging.The sensitivity and detection limit of miRNA-155 signal amplification system are significantly higher than that of ordinary signal amplification system.Compared with normal cells,the expression level of miRNA-155,one of the markers in tumor cells,is higher and affects cell function.By using the multiple structure of optimized nanomachines,multiple times and a large amount of miRNA-155 are collected while releasing a large amount of mirNA-apoptosis promoting apoptosis.To regulate the level of miRNA-apoptosis in tumor cells to inhibit cell activity and promote apoptosis.3.Peptide nucleic acid(PNA)A class of DNA analogs in which the glycophosphate backbone is replaced by a polypeptide backbone.Based on the characteristics that PNA/DNA binding has significantly higher free energy and unchain temperature than DNA/DNA binding,and PNA/DNA mismatch will lead to significantly lower free energy and unchain temperature,we designed a high-specificity single nucleotide signal amplification detection system that can distinguish tumor markers native ctDNA and mutated ctDNA with high specificity.It provides a reference for optimizing the specificity of amplification detection system and reducing the noise background signal.