Preparation,Characterization,Breast Cancer Imaging And Suppression Of Nucleic Acid Iron Nanocomposites

The remarkable increase in cancer incidence in the past few years has made it the second leading cause of death in the world after cardiovascular disease.Breast cancer is the most common cancer among women worldwide.Traditional treatments have certain drawbacks in terms of therapeutic effects and side effects.In recent years,nanotechnology has made significant progress in applications such as materials science,self-assembly,and drug targeted delivery.In particular,multi-functional nanomaterials have the potential to cancer diagnosis and treatment.Multi-functional nanomaterials have the characteristics of imaging diagnosis and targeted drug combination therapy,and have become a hot topic in recent years in the research and application of tumor diagnosis and treatment.Therefore,it is of great significance to explore breast cancer-targeted multifunctional nanocomposites as imaging-guided cancer therapeutics.This article reviews a variety of nanomaterials for tumor diagnosis and treatment,and their specific research and application in tumor imaging and treatment.Three different iron-based nanocomposites were designed and synthesized.The structures of nanocomposites were characterized by UV,fluorescence,infrared,Raman,X-ray photoelectron spectroscopy,scanning electron microscopy and transmission electron microscopy.The imaging properties and tumor inhibition effects of nanocomposites in vitro and in vivo were further studied.The main innovative results are as follows:（1）A novel nucleic acid ferromagnetic nanomaterial was synthesized by the coordination of nucleic acid with iron ions,the complementary pairing of base pairs and the coprecipitation method,which further self-assembled to be a multimodal imaging-guided gene therapy agent（BFe@DNA_H-siRNA）for breast cancer by electrostatic interaction with siRNA and dye.BFe@DNA_H-siRNA with specific target enhances cell uptake and achieves mitochondrial targeting of MCF-7 cells.At the same time,selective T₂ magnetic resonance imaging in mice further confirmed the good selectivity of BFe@DNA_H-siRNA for breast cancer cells.The loaded siRNA can interfere with the expression of hypoxia-inducible factor（HIF）in cancer cells,thereby achieving the purpose of inhibiting cancer cells.BFe@DNA_H-siRNA provides good protection for siRNA.From the anti-tumor effect of tumor-bearing mice,BFe@DNA_H-siRNA can inhibit breast cancer in animals.（2）A new nucleic acid ferrothermal nanomaterial（DNA-FeS₂）was synthesized by DNA template method,coordination and complementary pairing of base pairs,and its photothermal property and stability were improved by dopamine modification（DNA-FeS₂-DA）.DNA-FeS₂-DA further self-assembled with curcumin by electrostatic interaction into a novel imaging-guided photothermal-assisted natural drug-treated multifunctional nanomaterial（CUR@DNA-FeS₂-DA）.The special spatial structure and nucleic acid loading space provide the conditions for the successful loading of the natural drug curcumin（CUR）.Experimental studies have found that CUR@DNA-FeS₂-DA has good mitochondrial targeting and photothermal properties,and the loaded curcumin can interfere with the expression of pyruvate kinase M2（PKM2）and fatty acid synthase（FASN）in cancer cells.It inhibits the growth and proliferation of cancer cells and has no toxic side effects.Comparing the cell inhibition effect of CUR@DNA-FeS₂-DA in the presence or absence of near-infrared light,it further proved that CUR@DNA-FeS₂-DA has the characteristics of photothermal-assisted drug treatment.Therefore,CUR@DNA-FeS₂-DA can be used as an imaging-guided photothermal-assisted drug therapeutic for breast cancer.（3）A nucleic acid iron nanomaterial with excellent photothermal properties was synthesized by the coordination of nucleic acid and metal ions and layer by layer assembly,further self-assembled with CUR and andrographolide through electrostatic interaction,biomineralization and complementary pairing of base pairs into a novel mitochondria-targeted photothermal-assisted natural drug combination therapy agent（CUR@DNA-MnS@Fe-Andro）.The study found that CUR@DNA-MnS@Fe-Andro with good mitochondrial targeting and photothermal properties can interfere with the expression of UCP2 in MCF-7 cells and reduce the drug resistance of MCF-7 cells.Contrast experiments found that CUR@DNA-MnS@Fe-Andro under near-infrared light significantly enhanced its inhibitory effect on MCF-7 cells.Therefore,CUR@DNA-MnS@Fe-Andro can be used as a potential mitochondria-targeted photo-assisted natural drug combination inhibitor of MCF-7.