The Synthesis Of Chromium-doped Zinc Gallate Composite Nanofibers Gene Delivery Platform And Its Anti-Cancer Application Exploration

Tumor is a disease caused by abnormal expression of genes.Tumor development and metastasis are associated with a variety of tumor-associated genes.RNA interference(RNAi)is one of the gene therapy approaches and has attracted interest in cancer treatments due to its excellent anti-tumor properties.With the method of RNAi,to inhibit the activity of telomerase by targeting human telomerase reverse transcriptase gene,can effectively inhibit tumor growth.However,significant challenge remain in the ecient delivery of gene in vivo.Surface-modified gold nanorods are recognized as a promising gene delivery vehicle that can be loaded with negatively charged genes by electrostatic binding.Meanwhile,efficient gene transfection can be achieved by the unique surface plasmon resonance effect of gold nanorods.However,the technique suffers from relatively low targeting efficiency in cancerous tissue during blood circulation.Localized drug delivery systems are a means of administering drugs directly to the site of a lesion.It has many advantages,such as maximally stabilizing the activity of anticancer drugs,controllablely drug releasing,and can avoid drug waste and systemic toxicity.Therefore,combining localized drug delivery with gene therapy for gene delivery can reduce gene loss,increase local gene dosage,and achieve controlled release of genes.Chromium-doped zinc gallate material(ZnGa2O4:Cr,ZGOC)is a high performance gallate matrix luminescent material.When excited by excitation light,it can emit near-infrared spectra(600-800 nm)with high intensity.Also,this material can be excited by visible light,so a common LED can be used as a light source.In this paper,we designed a composite material based on chromium-doped zinc gallate nanofibers and gold nanorods for localized gene transfer,and at the same time to achieve photo-responsive release of genes under LED illumination.The main content lists are as follows:1.Preparation of chromium-doped zinc gallate nanofibers by sol-gel-electrospinning method.The preparation process of chromium-doped zinc gallate nanofibers was determined by exploring various factors,which are PVP,solvent composition,ion concentration,applied electric field and feeding speed.The obtained nanofiber has good crystallinity,no impurity phase,continuous morphology,uniform size and diameter of about 100 nm,and the nanofiber can be excited by ultraviolet light or visible light to emit near-infrared light of 600-800 nm..There are two sharp emission peaks at around 700 nm.The sintering temperature and the amount of chromium ion doping will affect the photoluminescence properties of the nanofiber:the higher the sintering temperature,the better the luminescence intensity;when the chromium ion doping amount increases,and the luminescence intensity first becomes stronger and then becomes weaker.When the doping amount is 0.5%,the nanofibers have the highest luminous intensity.2.Preparation of gold nanorods by silver ion-assisted seed growth method.The obtained gold nanorods have good dispersibility and water solubility.The surface modification and gene loading were carried out with gold nanorods with a maximum resonance absorption peak of 700 nm.Firstly,the gold nanorods were modified by PSS and PEI in layers,and gold nanorods with high surface positive charge density(Au-PEI)were obtained.Then negatively charged small interfering genes(siRNA)was successfully loaded on Au-PEI by electrostatic adsorption.In addition,Au-PEI has good gene loading performance,release performance and protective performance through agarose gel electrophoresis experiments.3.A composite nanofibers gene vector Au-PEI/siRNA@ZGOC with LED light responsiveness was constructed for localized gene delivery to liver cancer cells.The gold nanorods grafted with the interference gene were adsorbed onto the surface of the chromium-doped zinc gallate nanofibers electrostatically,and the composite ratio of the gold nanorods and the fibers was determined.Later,a series of biological experiments demonstrated that the composite fiber gene delivery vector has high gene delivery efficiency and excellent anti-tumor performance,and the gene silencing efficiency is increased from 40%to 65%.The mechanism by which LED light improving the gene interference of composite fibers is that the mild photothermal effect of LED illumination composite fibers in the tumor site:(i)promoting the desorption of the gene-loaded gold nanorods from the fibers;(ii)enhancing the fluidity of the cell membrane to promotes the uptake of gold nanorods by cells;(iii)promoting efficient escape of siRNA from endosomes.All three of these effects increase the accumulation of siRNA in the cytoplasm,thereby increasing the RNAi effect.