| Nucleic acid functional nanomaterials have many advantages such as molecular recognition ability,sequence designability and precise and material programmability,which have been extensively studied in the field of drug delivery.As an important branch of the field,DNA nanogels have been extensively studied in the biomedical field due to their designable nanostructures,controllable particle size,good biocompatibility and biodegradability.In this study,we focus on the preparation of magnetic DNA nanogels,drug loading and multistimuli-triggered release properties and the studies on the therapeutic effects of tumor cells.The main research work is summarized as follows:In chapter one,we summarized recent studies on nucleic acid-based functional nanomaterials for cancer therapy and classify them by cancer treatment methods(chemotherapy,gene therapy and immunotherapy).We further analyzed the function and characteristics of them in different therapeutic methods and how to construct nucleic acid functional nanomaterials and their functions by rational design and precisely regulate their functions as well as explained how nucleic acid functional nanomaterials can achieve drug loading and protection,targeted delivery and multiple stimuli-responsive.Finally,we pointed out the problems and challenges that nucleic acid functional nanomaterials need to overcome in clinical application transformation.In chapter two,superparamagnetic ferroferric oxide nanoparticles were synthesized and the surface of the nanoparticles was amino-modified.And then rolling circular amplification reaction carried out in-situ on the surface of the nanoparticles by using a synthetic circular DNA template to generate a large number of long DNA single strands and these DNA strands cross-linked to form the DNA nanogel layer.Thereby,we produced the magnetic DNA nanogel.The synthesis of magnetic ferroferric oxide,the modification of amino group on the surface of nanoparticles and the in-situ synthesis of DNA were demonstrated by a series of material characterizations such as TEM,SEM and DLS.The size of magnetic DNA nanogels was about 110 nm with the thickness of about 10 nm.They had good superparamagnetism and suitable nanometer size,which facilitated cellular uptake into cells.In chapter three,we utilized the magnetic DNA nanogel to load anticancer drug DOX.The drug nano-carrier had a high DOX loading efficiency due to the adsorption between DNA bases and DOX.The drug nano-carrier released the loaded DOX under multistimuli conditions,such as temperature,p H and nuclease,respectively.The release rate of DOX increased with the increasement of temperature and nuclease concentration and the decrease of p H,respectively.It demonstrated that this drug nano-carrier had the property of multistimuli-triggered drug release.In chapter four,the DOX-loaded magnetic DNA nanogels were studied for tumor cell therapy.The cellular uptake experiments proved that the nanomaterials rapidly entered into tumor cells within 12 h.They penetrated the surface tumor cells and reached into deeper cells under the constant magnetic field,which achieved targeted and three-dimensional drug delivery for better anti-tumor effect.The magnetic DNA nanogels had good biocompatibility,enriched and delivered DOX into tumor cells to achieve more effective therapeutic effect.This novel magnetic DNA nanogels not only served as good drug delivery carrier,but also had potential applications in magnetic resonance imaging.The construction of this hybrid material enriched the research of DNA functional materials and DNA nanogels,developed new utilization of DNA rolling circular amplification technology and expanded the application in biomedical fields. |
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