Selenium-containing Hyaluronic Acid Hybrid Nanogels For Tumor Therapy

Selenium is an essential trace element in human body,which participates in many physiological and biochemical functions.Selenium has a variety of physiological activities,including antioxidant,anti-aging,immune regulation,reducing the toxicity of toxic metal,scavenging free radical,protecting the liver,and auticancer.Comparing with inorganic selenium and organic selenium,red selenium nanoparticles have the characteristics of low toxicity and high biological activity,which are widely used in medicine and dietary supplement.Many studies have proved that selenium plays a vital role in cancer treatment and chemoprophylaxis.However,selenium nanoparticles are highly unstable and tend to slowly aggregate at room temperature.Therefore,it is very necessary to apply stabilizers to maintain the physical and chemical stability of Selenium nanoparticles.For exmple,surfactants(such as PVP,SDS-PEG etc.),polysaccharides(chitosan,hyaluronic acid,etc.)and bovine serum albumin,are common stabilizers.Hyaluronic acid(HA)is an anionic polysaccharide with carboxyl and hydroxyl group.It can specifically bind with the CD44 receptor that some cancer cells overexpress.Due to the above characters,HA often performs as drug carrier to deliver anti-tumor drugs to tumor tissues where the cells have high expression of CD44,and in this way the selective distribution of drugs in tumor area is improved and so as to the antitumor effect.In this paper,by employing HA as the basic framework,we prepared selenium-containing HA hybrid nanogels for drug delivery system.More contents of this paper are as follows:1.Preparation of Se-containing hyaluronic acid hybrid nanogelsIn this paper,we use dopamine(DOPA)and methacrylic anhydide(MA)to modify the skeleton of HA to get MAHA-DOPA,and after utilizing,EGDMA as the crosslinking agent,sodium selenite as the precursor solution of selenium nanoparticles,vitamin C as reductant and 4,4'-azo-bis(4-cyano-pentanoic acid)(ACVA)as the initiator.Se-containing HA hybrid nanogels(Se@NGs)were successfully synthesized by free radical polymerization.The particle size of Se@NGs was about 200 nm,and the surface of Se@NGs are negative charged.By transmission electron microscopy(TEM),we can observe that Se@NGs are in spherical shape and uniform distribution and have core-shell structure.Besides,They are also well dispersible in some dispersion medium.2.Pharmacodynamic evaluation of Se-containing HA hybrid nanogelsThe as-prepared Se@NGs are able to load the poorly soluble DOX and ICG to form Se@NGs/DOX/ICG.The loading rates of DOX and ICG were about 6.3% and 5.9%,respectively.In pH 7.4 phosphate buffer,the cumulative release content of DOX was about 20% in 72 hours,while in pH 5 acetate buffer,the cumulative release was up to 40% in 72 hours.It is showed that Se@NGs have negligible cytotoxicity.Finally,Se@NGs to some extent have certain inhibition effects on cancer cells and will get more powful inhibition effects when loading DOX,ICG,or both,besides,the rate of inhibition rises markedly by irradiated of 808 nm near infrared lase.