Preparation And Bio-application Of Water-soluble Conjugated Material/Hyaluronic Acid Composite Nanomaterials

Water-soluble conjugated materials have been widely used in biological detection,analysis,imaging,and therapy because of their good optical properties and water solubility.Hyaluronic acid is a natural macromolecular polysaccharide with a large amount of negative charge,good biocompatibility,multiple chemical sites available for modification,and can target tumor cells via CD44 receptors.Water-soluble conjugated materials and hyaluronic acid are combined to form composite nanomaterials,which can increase the targeting and biocompatibility of water-soluble conjugated materials in organisms,reach tumor tissues through active and passive targeting in vivo,and achieve fluorescence imaging or treatment of the tumor.Early diagnosis and monitoring of cancer therapy is the key to cancer treatment,so the development of multifunctional nanomaterials(simultaneous imaging and therapy)using simple preparation method is of great significance.In this paper,two different methods are used to combine the water-soluble conjugate materials and hyaluronic acid to obtain nanomaterials:1.Hyaluronic acid(HA)and a conjugated material with two-photon absorption(BFVPBT)are connected by a disulfide bond to obtain an amphiphilic polymer HA-SS-BFVPBT,and then a selfassembly strategy is adopted to prepare the nanoparticles containing anticancer drug camptothecin.The effects of grafting degree of conjugated materials on the nano-materials were studied.This method avoids the multiple modifications of HA and can prepare nanoparticles more easily than the traditional methods.The prepared nanoparticles could load non-water-soluble drugs in hydrophobic cavities,and target to tumor cells for fluorescence imaging and treatment.In addition,the linker between the hydrophobic moieties and the hydrophilic macromolecules were reductive response type bond——disulfide bonds,which could be reduced in tumor cells because of the reducing environments;moreover,hyaluronidase is also overexpressed in tumor cells that could degrade the hyaluronic acid to control the release of drugs.In the two-photon laser confocal fluorescence imaging of human cervical cancer cell Hela,the nanoparticles exhibit good imaging effect and photostability.2.The thiolated hyaluronic acid was prepared by grafting thiol groups on hyaluronic acid,which can self-crosslink the nano-water core generated by the water in oil(W/O)nano-emulsion method to obtain nano-gel.The nano-gel can load the water-soluble conjugate material(PPE)and anticancer drug doxorubicin hydrochloride,providing targeting for the water-soluble substances wrapped in the nano-gel and prolonging circulation time in vivo.The nano-gel can be degraded in a tumor reductive environment to release the encapsulated imaging agents and drugs.The morphology,reductive response and spectral properties of nano-gel were studied,and laser confocal fluorescence imaging results of Hela cell proved that the conjugated material encapsulated in the nano-gel exhibited better imaging effect.