Design,Preparation And Application Of Cationic Polymer/Silica Composites As Drug/Gene Vectors

Silica nanopraticles have been widely studied in biomedical fields as safe and efficient gene/drug carriers because of their controlled morphology and size,high specific surface area,easy surface modification and good biocompatibility.However,bioaccumulation limits the application of silica nanomaterials.Therefore,we prepared biodegradable silica nanoparticles,which are assembled with cationic polymers to construct drug and gene co-delivery carriers.The degradation of carriers can reduce the accumulation in vivo,reduce toxicity and promote gene and drug release.In addition,the surface morphology of silica nanoparticles can affect their interaction with cells and organisms,spike-like silica can increase the adhesion of the membrane,and promote cell endocytosis.Gold nanorods(Au NRs)demonstrate photothermal effects and possess the functions of CT and photoacoustic imaging.In this paper,gold nanorods grow in the capsule of spike-like hollow silica nanoparticles,and cationic polymers are assembled on the surface to construct a multifunctional carrier with photothermal response,which can be combined in a variety of ways.Detailed works are as follows.1.The biodegradable drug-loaded silica nanoparticles(DS-DOX)were synthesized by introducing a drug disulfide(DOX)and a redox-responsive disulfide bridged silane coupling agent(BTOCD).In order to realize the codelivery of genes and drugs,the surface of DS-DOX nanoparticles is readily functionalized with the assembled polycationic CD-PGEA,comprising one-cyclodextrin core and two ethanolamine-functionalized poly(glycidyl methacrylate)arms,to achieve DS-DOX-PGEA.The in vitro and in vivo degradation behaviors were studied by comparing silica nanoparticles(DS)containing disulfide-containing disulfide bonds and ordinary silica nanoparticles(SiO2).At the same time,the combined therapy was studied by in vivo and in vitro experiments.The results show that DS-DOX is more easily to eliminate from the body,and is more likely to be excreted than SiO2.In addition,drug-embedded biodegradable silica can promote cell endocytosis,improve gene transfection and provide a better therapeutic effect in the treatment of cancer.2.The spike-like hollow silica nanoparticles(HSN)were synthesized by template method.The Au-HSN was obtained by growing the gold rod in the HSN cavity by seed-mediated growth method.Then,the surface of Au-HSN was modified with cationic polymer(CD-PGEA)to obtain the near infrared light responsive gene and drug co-delivery carriers(Au-HSN-PGEA).The Au-HSN-PGEA loaded with anticancer drug sorafenib(SF)was used to study combined multi-method therapy of liver cancer.The results showed that Au-HSN-PGEA had good encapsulation ability to combine pDNA and demonstrated high gene transfection efficiency in HepG2 cells compared with PEI and lipo2000.It is also proved that Au-HSN-PGEA has good photothermal effect and the temperature will rise rapidly under the near infrared irradiation.In addition,as a good drug carrier,the Au-HSN-PGEA can achieve near-infrared response to control drug release.