A DNA/upconversion Nanoparticle Hybrid Nanogel For Real-time Quantitative Monitoring Of Drug Release

Recently,DNA hydrogel has been increasingly studied as drug carrier.However,the pharmacokinetics studies of DNA hydrogel in biological environment need to be further researched.The real-time information,such as the cumulative drug release,will help us to better understand the drug release kinetic studies,but how to accurately monitor the real-time information in vivo is still a great challenge.In the first chapter,the synthesis method of DNA hydrogel was divided into three categories: the assembly of branched DNA,the entanglement of ultra-long DNA chains and the hybridization of DNA with other materials.Importantly,the hybridization of functional nanomaterials could easily endow DNA hydrogel with functions,which had great potential in biomedical applications.In the second chapter,the ultra-long single-stranded DNA was synthesized by rolling circle amplification;the upconversion nanoparticle(UCNP)was synthesized by solvothermal method;DNA/upconversion nanoparticle hybrid nanogel(UCDN)was prepared by intertwining DNA on the surface of UCNP.In the third chapter,the properties of UCDN was optimized.The upconversion luminescence(UCL)intensity was controlled by regulating the ratio of doped lanthanide ions in UCNP,and the UCNP with uniform intensity of UCL peaks was selected for ratiometric imaging.On the other hand,different UCDNs were synthesized by regulating the addition amount of DNA,and the UCDN with high luminous resonance energy transfer(LRET)efficiency was selected for ratiometric imaging.In the fourth chapter,based on the programmability of DNA,the ultra-long single-stranded DNA containing aptamer AS1411 was synthsized to prepare UCDN.Through cell uptake and flow cytometry experiments,it was proved that the UCDN with AS1411 aptamer had a great specific targeting to human breast cancer cell MCF-7.In the fifth chapter,by utilizing the LERT between UCNP and chemotherapy drug mitoxantrone(MTX),the real-time quantitative release of MTX could be monitored by measuring UCL signals in mouse model.The ratiometric imaging method used NIR emission as internal reference to get the relative intensity of red emission.Compared with single emission imaging,this method effectively avoided the influence of internal microenvironment and local material concentration,and achieved accurate and reliable monitoring of cumulative drug release in vivo.In summary,on the basis of DNA hydrogel as drug carrier,this paper reported a UCDN as drug carrier,and used it for real-time quantitative monitoring of drug release in vivo by ratiometric imaging.