Preparation And Application Research Of Composite Nanoparticles Contained Gold Nanorods

In recent years, gold nanorods (GNRs) have appealed mounting attention due to their unique structure and functional characteristics in biomedical field. GNRs have controllable size and optical properties, which promoting their application in biological imaging and sensor. The longitudinal surface plasmon resonance wavelengths (LSPRW) of GNRs can be adjusted to the near infrared region, so GNRs can convert light energy into heat energy efficiently, and it has a potential application in cancer therapy. GNRs are synthesized through the seed-mediated growth method, therefore, mesoporous silica-coated GNR (GNR@mSiO2) can reduce the toxicity, improve the stability and make for further modified. The temperature responsive composite nanoparticles have attracted more and more attention due to their drug targeted delivery applications. Based on this research background, we firstly studied the mechanism of fluorescence enhancement and quenching; secondly, we prepared two different temperature sensitive composite nanoparticles, thermosensitive liposomes and temperature sensitive polymer, which have the application in tumor treatment. We combined photothermal material (GNR) with temperature responsive nanoparticles, and realized controlled drug release. Based on storehouse mesoporous channels, high loading capacity could be achieved. Temperature stimuli acted as a trigger, controllable drug release in human body and near infrared illumination conditions can be actualized. The results of each part are listed as follows:(1) First, cetyltrimethyl ammonium bromide stabilized GNRs were synthesized through the seed-mediated growth method, and a layer of adjustable thickness of mesoporous silica structure was encapsulated around GNR via improved stober method. The mechanism of fluorescence enhancement or quenching was studied. We found that the distance between GNR surface and fluorophore, the distribution of fluorophore in mesoporous silica and the kind of fluorophore were three main reasons responsible for the fluorescence change. GNR@mSiO2-fluorophore has the stronger excited fluorescence than fluorophore alone, which leading fluorescence labeling has potential application in bioimaging, biosensors, biological detection.(2) Base on the study of gold nanorods and GNR@mSiO2, a kind of thermosensitive liposome contain gold nanorods, GNR@mSiO2-supported lipid bilayers(GNR@mSiO2@SLB) composite nanoparticles were prepared for controlled drug release. The different molar ratio of raw materials could change the phase transition temperature in liposome preparation, and finally we chose the system 7:2:1. We proposed four methods to synthesis, and ultimately selected film hydration method to prepare thermosensitive liposome nanoparticles. GNR@mSiO2@SLB nanoparticles presented many advantages, such as photothermal, targeting and themperature sensitive properties, which can realize controlled release drug. Experimental results showed that doxorubicin(DOX) could be effectively loaded into GNR@mSiO2@SLB composite nanoparticles with 31.4%±1.5% loading capacity and 62.8%±3.0% encapsulation efficiency. The cumulative release of DOX-loaded nanoparticles indicated that it was temperature dependent. After 24 h, the drug release for GNR@mSiO2@SLB-DOX at 37℃ was 7.2%, whereas the drug release at 43℃ was 46.9%, which was 6.5 times as the former.(3) We prepared poly(N-vinylcaprolactam-co-hydroxypropyl methacrylate) (P(VCL-co-HPMA)) shell coated gold nanorod@mesoporous silica (GNR@mSiO2) through precipitation polymerization. The temperature sensitive composite microspheres can be applicated in drug controlled release due to their thermal properties, mesoporous porous and temperature response. Moreover, we can change the ratio between VCL and HPMA to adjust the volume phase transition temperature (VPTT) of the polymer. When temperature rised, polymer shell shrinkaged, and the size of composite microspheres was getting smaller, thus the loaded drug can be released. Experimental research results showed that the composite microspheres had 15.5±0.6% loading capacity and 67.2±3.0% encapsulation efficiency, and the drug release was temperature dependent. When the surrounding temperature was lower than VPTT, the drug release rate was slow, but when the temperature was higher than VPTT, the release rate was much faster. This characteristic made the composite microspheres have potential application in the treatment of tumor.