Drug Carrier Construction And Toxcicity Studies Based On Zeolitic Imidazole Framework-8(ZIF-8)

With the development of nanotechnology and its penetration to the medical field,the nano technology has opened up a new way for the treatment of tumor,the construction effective nanoparticle drug delivery system is of great significance for cancer therapy.By using nanomaterials as delivery carriers,The therapeutic effect of the drugs can be greatly improved,and adverse side effects of the drugs be reduced.At the same time,the stability of the drug molecules can also be increased due to the protection of the carriers.Currently,common drug carriers include carbon nanoparticles,liposomes,silica nanoparticles,etc.Among all of them,Metal-Organic framework materials(MOFs)which comprised of inorganic metal ions or metal clusters linked by organic ligands through coordination bonds have attracted much attention in gas storage and separation,detection,catalysis,biomedical and other fields,due to its chemical component diversity,adjustable structure,pore tunability and easy modification.Especially in the field of biomedical drug delivery applications,the selectivity of metal-organic framework materials component is advantageous to the preparation of biocompatibility material.Adjustable structure and easy modification of MOFs are beneficial to effective load and controlled release of drugs.The unstability offers the possibility to the biodegradable of materials.So,Metal-organic framework materials showed an attractive application prospect in the field of drug delivery.Although MOFs based drug carrier have shown good performance in drug loading release,the cytotoxicity of material and drug controlled release behavior of the materals are rarely involved.In respect of the issues above,aiming at the exploration of novel drug delivery carriers,we are expected to construct a new class of drug controlled release system based on zeolitic imidazole frame work-8(ZIF-8)which is characterized of its facile preparation,biodegradable,high load ability,high porosity and degradeble in aci.dic environment.Based on this,we also preliminary studied the cytotoxicity and toxicity mechanism of ZIF-8 nanoparticles.The main research aspects are as follow:1.Indocyanine green-encapsulated Metal-organic framework nanoparticles for cancer image and photothermal therapy.As a widely-adopted agent for near infrared imaging and photothermal therapy(PTT),Indocyanine Green(ICG)remain problematic due to the instability and easy to removal by the body ect.To address this problem,we here proposed one-pot synthesis method of ICG@ZIF-8 NPs through the coating of a ZIF-8 nanoshell outside the ICG molecules.In this system,ICG molecules were encapsulated in ZIF-8 in one-pot method.At neutral pH,ICG was limited in internal pores and are not able to leak out from ZIF-8.While exposure to the acidic environment in tumor site,ZIF-8 is self-degraded,leading to the ICG release.On one hand ICG is a kind of near infrared dye for cancer imaging which was approved by Food and Drug Administration(FDA).On the other hand it can convert light energy to heat leading to a photo-therapeutic effect.In vitro results demonstrated ICG@ZIF-8 nanoparticles possess anti-light-induced bleaching ability,good thermal stability and great photothermal conversion effect under NIR light irradiation.Further experiments suggest that ICG@ZIF-8 nanoparticles possess efficient near infrared imaging and tumor cell kill effect.ICG@ZIF-8NPs developed here might be the important supplement of drug delivery nanocarriers and show a potential to provide a wide range of approaches for tumour imaging and therapy fields.2.Cytotoxicity studies and toxicology research of Zeolitic imidazole framework-8(ZIF-8)nanoparticlesAlthough the ZIF-8 nano-carrier possess good stimulation response behavior,its biocompatibility is a critical factor before implementing clinical application.To study the cytotoxicity of ZIF-8 nanoparticles,in this work we synthesized different size of ZIF-8 particles and carry out our research by incubating the particles with SMMC-7721 cells.We also preliminarily explored toxicity mechanism of ZIF-8 nanoparticles by Oxygen Species(ROS)staining.The results show that the larger particles tend to have high cytotoxicity.But particles synthesized from different solvent have the almost same influence to cytotoxicity.Toxicity mechanism study demonstrated that ZIF-8 nanopatucles can cause a lot of ROS which leads to apoptosis.