A Novel Magnetic System-Janus Infrared Response Nanocarrier Targeted Drug System And Its Anticancer Effect

Background:Because the blood-brain barrier?BBB?can prevent most anti-cancer drugs from entering the brain,chemotherapy for malignant gliomas or other brain metastases is greatly limited.Therefore,research and development of drugs that can pass the blood-brain barrier or their carriers have become the key and hot spot for improving the therapeutic effect of intracranial malignant tumors.In view of the physical principle that magnetic particles prepared by Janus nanomaterials can be oriented in a magnetic field,it is possible to develop a novel magnetic-oriented drug carrier for targeted therapy of malignant tumors,thereby greatly improving the chemotherapy effects of malignant tumors.Objective:?1?.Preparation of a novel magnetically-oriented drug carrier-ball-column Janus infrared-responsive nanomaterial,which can be guided by magnetic force after iron ion modification,and the drug can be controlled to release under the infrared thermal effect;?2?.Using 3D printing technology to customize the suitable 3D external magnetic device,constructed a new magnetic-Janus infrared response nanocarrier targeting drug system,and verified the efficiency of drug targeting transport of the new carrier system;?3?.The cytotoxicity and tumor-bearing nude mice experiments were carried out to verify the targeted drug delivery ability and the chemotherapy effect on malignant glioma,and provide theoretical and practical guidance for subsequent technology development and clinical application research.Methods:?1?.Designed and improved the manufacturing process of silicon-coated gold,prepared a new ball-column Janus infrared-responsive nanomaterial,and obtained magnetic properties after modification with Fe₃O₄;adsorbed the anticancer drug DOX to Janus nanoparticles and wrapped it in l-tetradecyl alcohol to obtain Drug Janus nanoparticles;scanning electron microscopy and transmission electron microscopy observation of the characterization of the Janus nanomaterials;?2?.The Janus silicon gold-bonded material prepared by the new method and the traditional gold rod were placed in pure water for infrared excitation temperature experiment,and the heating rate and drug release efficiency of the two materials were observed.The U251,HBE and A549 cells were used for in vitro cytotoxicity experiments.Analyze and compare the cytocompatibility of each material;?3?.A BBB model consisting of gelatin and brain microvascular endothelial cells was constructed in Transwell chamber.The effect of magnetic force on the efficiency of the new Janus material structure penetrating the BBB model was observed in vitro.?4?.Lentiviral transfection was used to construct LUC-GFP-U251 cell line for the preparation of tumor-bearing nude mice.One week later,the drug-loaded magnetic-Janus infrared-responsive nanoparticles were injected into the tail vein,and the mice were fixed under a 3D external magnetic device.Targeted drug therapy,4 times a week for 3 weeks,the small animal live imager continuously observed the growth and changes of the tumor.At the end of the 4th week of the experiment,the animals were killed and the blood and heart,liver,spleen,lung and kidney tissues of the mice were collected for liver and kidney function and routine pathological examination.?5?.Statistical analysis of data,comprehensive evaluation of the targeted transport efficiency and anti-cancer effects of new drug carriers.Results:?1?Scanning electron microscopy showed that the new Janus silicon-bonded gold nanoparticles were spherical-rod structure and shaped like a loquat;After Fe₃O₄modification,Fe₃O₄ wrapping around the Janus structure was observed under transmission electron microscopy;?2?Infrared heating experiments show that the Janus particles have higher heating efficiency than the gold rods.After the Janus particles were loaded with DOX,the heat release of the drug can be excited by infrared interval,and the drug release curve rises in a gradient.The in vitro cytotoxicity experiment indicated that the Janus system had an excellent cell compatibility;?3?The transwell chamber BBB model verified that the magnetic permeability of the magnetic Janus system was the highest under the attraction of the external magnetic field,indicating that the magnetic force was the key factor for the carrier to pass through the BBB model;?4?The small animal live imager monitored the fluorescence dynamics of the tumor-bearing nude mice for 1⁴ weeks.The tumor model was successfully constructed.The therapeutic effect of each group was evaluated after 3 weeks of targeted therapy.The anti-tumor effect of JGSMD+external magnetic device+near-infrared irradiation group is the best.Conclusion:?1?In this paper,a new Janus silicon-bonded gold nanomaterial with a ball-rod structure was successfully fabricated by improving the silicon-coated gold process.The Janus material has better penetrability,photothermal response effect and lower cytotoxicity.?2?The addition of Fe₃O₄ to Janus silicon is a magnetic-Janus infrared-responsive nanocarrier-targeted drug system that can be transported to the tumor site under the guidance of a 3D external magnetic device.The targeted therapy of tumor-bearing nude mice showed a well anti-tumor effect.