Preparation And Properties Of Magnetic-based Prussian Blue Multifunctional Drug Carrier

The current method of tumor treatment is single,usually unable to meet treatment needs.The traditional chemotherapy,radiotherapy and other clinical treatments have enormous toxicity,and damage to normal tissues and organs.In recent years,the rapid development of nanomedicine and biotechnology has brought a new revolution to cancer treatment.The emergence of drug delivery system provides a new way for the targeted transport and controlled release of drugs,and effective treatment for cancer.And the reduction of toxic side effects to the body are of great significance.At the same time,in order to improve the life quality of cancer patients,non-invasive cancer treatment technology has become a hot research topic at home and abroad,and new methods such as photothermal therapy and photodynamic therapy have emerged.Therein,the novel nano-drug carrier based on photothermal therapy has become the focus of researchers.The carrier can not only achieve drug loading and sustained release,but also realize selective accumulation in the tumor site,and can efficiently transform under the condition of implementing near-infrared illumination.The ultra-high temperatures were produced at tumor site,which can easily ablate the tumor.With the deep interdiscipline of biomedical and nanomaterials,researchers have developed a number of new nanomedicine carrier materials,such as ferrite,sulfide,gold,carbon,polymers,etc.,however,there are not many materials currently approved for clinical application.Fe₃O₄ is a low-toxic inorganic material with good biocompatibility.Phillips magnetic developed by Bayer Schering and other companies has been used as an MRI agent.Prussian blue?PB? is an antidote to clinical treatment of sputum poisoning approved by the US Food and Drug Administration?FDA?.Long-term clinical practice data have proven that PB has excellent biosafety.Recent studies have shown that PB nanomaterials have superior absorption in the near-infrared region and have high photothermal conversion efficiency,which is an ideal candidate for photothermal therapy.At present,the comprehensive utilization of nanomaterials already in clinical application is an important direction of current biomedical concerns.In this paper,Fe₃O₄@PB composite microspheres were used as research objects to develop an integrated nano drug carrier with imaging and magnetic targeting functions.The Fe₃O₄ core acts as a agent and MRI contrast agent to achieve targeting and imaging functions.The mesoporous structure of the Fe₃O₄ core were used to load anticancer drugs.The same time,the PB outer shell is used as a photothermal conversion agent,in order to realize the drug and photothermal synergistic treatment of mesoporous Fe₃O₄@PB composite microspheres on tumor cells.The main research is as follows:?1?Firstly,using ferric oxide microspheres as a template,based on the formation reaction of PB,the Fe₂O₃ microspheres were used to slowly release Fe³⁺ in an acidic solution.The PB shell in the acidic solution was studied in the ferric oxide.Feasibility and control factors of surface deposition of microspheres.Systematic experimental studies have shown that the release of iron ions from Fe₂O₃ microspheres in acidic solution can achieve the formation of PB,but the release rate of ferric ions in the pure water system does not match the diffusion rate of ferrocyanide ions,among which ferric ions the excessive release rate leads to PB homogeneous nucleation.By regulating the composition of the reaction system solution,the introduction of ethanol successfully inhibits the ionization of hydrochloric acid,slows the release rate of iron ions,the same time,the ionization of K₄[Fe?CN?₆] was successfully inhibited and the release rate of[Fe?CN?₆]^4- was slowed down.So realizes the controllable formation of PB shell on the surface of Fe₂O₃ microspheres.The subsequent dissolution of the residual Fe₂O₃ microspheres achieved the controlled synthesis of uniform monodisperse PB hollow microspheres.Drug-loaded and photothermal experiments showed that PB hollow microspheres had a drug loading of up to 440 mg/g for DOX drugs and infrared light with a density of 1 W for 808 nm for a solution system with a concentration of 200?g/mL.In minutes,the temperature can be raised to 75.9?,showing excellent photothermal conversion efficiency and photothermal stability.With Hela cells as the research object,the PB hollow microspheres have good biosafety and the concentration of 50?g/mL dose was used to synergistically kill cancer cells by photothermal and drug synergy is 60%.?2?Based on the experimental results of the previous chapter,using Fe₃O₄ microspheres as Fe³⁺ precursors and superparamagnetic Fe₃O₄ microspheres as templates,Fe₃O₄@PB composite microspheres with magnetic targeting and MRI imaging functions were developed.Experimental results indicate that the dissolution of Fe₃O₄ microspheres in acidic solution is different from that of Fe₂O₃ microspheres.The small particles inside Fe₃O₄ microspheres are preferentially corroded.At the same time as the formation of PB shell,mesoporous structure is formed inside Fe₃O₄ microspheres.The Fe₃O₄ microsphere core not only retains the original Fe₃O₄ performance,but the mesopores provide storage space for the DOX.The results show that the mesoporous Fe₃O₄@PB nanocomposite microspheres have a drug loading of 320 mg/g.When the concentration is 200?g/mL,the temperature rises to 63.1? and maintains good photothermal stability at a concentration of 50?g/mL dose,the synergistic effect of killing cancer cells by photothermal and drug synergy is more than 55%;In addition,Fe₃O₄@PB composite microspheres have a saturation magnetization of 23 emu/g,which has potential magnetic targeting function and can be used as MRI imaging.Contrast-assisted therapy is an ideal nano-drug carrier for diagnosis and treatment.