| With the development of nano technology, a growing number of nano-drugs for cancer treatment were developed.Because of the highly controlled structure, inorganic nanoparticle has a very important position in the construction of nano-drug. Silica nanoparticles(SNPs) possessing easy fabrication, largesurface area, low toxicity and easy functionalization propertieshave been widely used as thematrix for biological applications.However, these silica based systems generally just depend on chemotherapy to realizethe therapeutic goal, which will be uselessformulti-drug resistant(MDR) cell lines.Because the inorganic nanomaterialis unable to be biodegraded, large amount of SNP will cause serious material bio-fouling.In order to overcome this shortage, we have designed a chemo-photothermal therapy nanomedicine with silica coated gold nanorods(GNR@Si O2).GNRhave beenwidely applied in photothermal therapy which was recognized as the most potential adjuvant therapy.The outer mesoporous Si O2 shell exhibits the potential for allowing a high drug payload, thus posing itself as an effective drug carrier. Additionally, the protection of the silica shell guarantees the utilization of the NIR-transparent window provided by the GNR core in complex biological environments.The photothermal effect of GNR can greatly enhanced the drug accumulationin MDR cell and their sensitiveness todrugs, which can improve the overall treatment efficiency. Because the drug release isp H sensitive, accurate p H measurement of the local environment that the SNP experienced upon cellular internalization is indeed necessary.For this purpose silica based p H nanosensors were prepared and studied. The following workhas beencarried out.(1) The preparation procedureof SNP p H nanosensors can be described by threesteps, amination,polymer coating and dye conjugation. SNP was synthesized by St?ber method. And then, amination of SNPs wascatalyzed by acid.Two polymers, methoxypolyethylene glycols(m PEG)and hyaluronic acid(HA) were used for SNP coating. PEGylationand HA modification can greatly enhance the bio-stability andbiocompatibility of particles. Threefluorescent dyes were conjugated with SNPs via covalent bond tobuild a ratiometric fluorescent p H sensor, which can minimize theleaching of dyes from nanoparticles. The dynamic p H measurementrange was extended to p H 3.8–7.4 which could cover almostall physiological conditions, especially the endosomal–lysosomalsystem. The polymer modification offers the nanosensor remarkable colloidalstability which was crucial for living cell measurement.(2) The GNR with desirable NIR excitationwindow(LSPR absorption peak at 750-800 nm) was prepared by silver mediated seed growth method. Subsequently, silica was coated on the GNR by modified St?ber method to form a mesoporous silica shell(about 30 nm).After functionalizedwith carboxyl, anticancer drugs were loaded by electrostatic interaction. Alkylatedcoumarin, whichwas an ideal photo-trigger, was used to realize the drug encapsulationand controlled release. At last, polymer(F127) and targeting molecule were assembled to give the nano-drug colloidalstability and targeting effect.The results indicated that the prepared nano-drug can efficiently transform the energy of light into heat. With irradiated under a 1 W NIR laser,the system temperature has been promoted from 25℃ to 41℃in 8 min. The drug wasperfectly encapsulatedby oily layer which was formed by alkylatedcoumarin. The drug release rate was also obviously increased after exposure to NIR laser. |
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