Preparation Of Hollow Type Fe₃O₄@mSiO₂-AuNCs Composite Microsphere And Its Application In Drug Delivery

At present,the theranostic composite microspheres have attracted more and more attentions because of their multifunctions such as targeting drug delivery,multi-therapies?chemotherapy,thermotherapy,photodynamics therapy?and imaging?fluorescence imaging,magnetic resonance imaging?.In the field of biomedicine,superparamagnetic Fe₃O₄ nanoparticles are often applied in magnetic separation,magnetic targeting,magnetic hyperthermia and magnetic resonance imaging.Mesoporous silica?mSiO₂?is usually used as drug delivery due to its easy functionalized surface,adjustable pore size,and biocompatibility.Gold nanoclusters?AuNCs?applied as fluorescent labels and fluorescent imagings are of excellent fluorescence properties,good bleach resistance and biocompatibility.In general,as a drug delivery system,the cavity structures of the composite microspheres are able to increase the drug loading capacities and deliver sufficient drugs to tumor sites.Basing on above-mentioned advantages,we synthesized a novel structure of hollow type Fe₃O₄@mSiO₂-AuNCs composite microspheres in this article.The results were described as follows:1.Preparation of Fe₃O₄/polystyrene?PS?composite microspheresFe₃O₄ nanoparticles were synthesized by solvothermal method with the modification of polyvinylpyrrolidone?PVP?and polyethylene glycol?PEG?,respectively.The results indicated that Fe₃O₄ nanoparticles modified by PVP and PEG were of monodispersity as well as the adjustability of particle size.For the synthesis of Fe₃O₄/PS composite microspheres by soap-free emulsion polymerization,the particle sizes of Fe₃O₄/PS microspheres could be controlled by adjusting the amount of styrene,the ratios of comonomer acrylic acid and the crosslinker divinylbenzene.And the weight loss of PS layers in these composite microspheres could be controlled between 18-76 wt%.2.Preparation of hollow type Fe₃O₄@mSiO₂ composite microspheresThe Fe₃O₄/PS@SiO₂ composite microspheres were obtained by coating SiO₂ on the surface of Fe₃O₄/PS composite microspheres by sol-gel method.Abundant porous structures could be obtained by adjusting the amount of the mesoporous template agents.The cavity templates?PS microspheres?and the mesoporous template agents were removed by calcining at a high temperature to form hollow type Fe₃O₄@mSiO₂composite microspheres.It was found that the cavity structures increased the BET specific surface area and the BJH pore volume of the composite microspheres,but the composite microspheres were of positive charge,which limited their application in biomedical engineering.3.Preparation of hollow type Fe₃O₄@mSiO₂-AuNCs composite microspheresHollow type Fe₃O₄@mSiO₂-AuNCs composite microspheres were prepared by connecting AuNCs with amine-functionalized hollow type Fe₃O₄@SiO₂ composite microspheres.The results showed that the charge of the composite microspheres changed from positive to negative after the modification of gold nanoclusters,which indicated that the hollow type Fe₃O₄@mSiO₂-AuNCs composite microspheres were biocompatible.4.Research on drug delivery of hollow type Fe₃O₄@mSiO₂-AuNCs composite microspheresThe drug loading and releasing properties of hollow type Fe₃O₄@mSiO₂-AuNCs composite microspheres were investigated using hydrophobic Ibuprofen as drug model.The effects of times,temperatures and pH values on the drug loading capacities of hollow type Fe₃O₄@mSiO₂-AuNCs composite microspheres were discussed.The results showed that the optimized drug-loading conditions were the time of 30 min,the temperature at 45°C and pH value of 6.6.Under the optimized conditions,the maximal drug loading capacity could reach to 24.9 mg/g.In addition,this paper also discussed the release properties of drug-loaded hollow type Fe₃O₄@mSiO₂-AuNCs composite microspheres under different pH values.The results showed that the weak acidic solution was favorable for the drug release from the composite microspheres.