Synthesis Of Azobenzene Derivatives-based Nanoassemblies And Their Applications In Controllable Drug Release System

In recent years, controlled release drug system(CRDS) has shown great potentials in diagnosis and treatment of cancer with the development of nano-materials and technology. CRDS contains the anti-cancer drug and the responsive carrier, which can release drugs at diseased region when triggered by pH, temperature, light or enzyme. Through the functional modification of the drug carrier with responsive groups, the drugs can be accurately released at desired time and site, which can effectively reduce the early release of drugs, decrease the loss of drugs in transport, which has important research significance in biomedical field. Azobenzene derivatives have attracted increasing attentions in light-controlled drug delivery systems due to its excellent photoisomerization properties. However, the early studies on light-responsive CRDS mainly use ultraviolet sources for the activation, which leads to the limited penetration depth and high toxicity to cells. In order to solve these problems, two series of azobenzene derivatives based drug nanocarriers were designed and successfully synthesized, which are responsive to two-photon near infrared light and chemiluminescence. The main results are briefly summarized as follows:(1) The synthesis, characterization and the two-photon near infrared responsive properties of azobenzene-containing hyperbranched molecule assemblies(HPGAZO) : A novel two-photon-triggered amphiphilic hyperbranched polyglycerol micelles(HPGAZO) were designed and successfully synthetized, which contains different rod(hydrophilic azobenzene) and coil(lipophilic polyglycerol) segments. HPGAZO nanoparticles showed good biocompatibility and monodisperse property, HPGAZO is about 66 nm in aqueous solution. Under the irradiation of 720 nm two-photon pulsed lasers, trans-azo groups transform to cis-azo groups of HPGAZO which lead to the damage of structure of HPGAZO micelles.The basic properties of HPGAZO were carefully studied, including photo physical properties, the self-assembly behaviors and two-photon response property. The result shows that HPGAZO have good water solubility and dispersibility, which can be used as a potential drug carrier.(2) The synthesis and characterization of self-assembled nanoparticles formed by host-guest interaction between the cyclodextrin and azobenzene: A water-soluble polymer(PAZO) by connecting polymaleic anhydride with azobenzene-containning(AZO) side chain via an amide bond were designed and synthetized; another water-soluble polymer(PCD) by connecting polymaleic anhydride with amino cyclodextrin(AZO) side chain were also synthetized. A novel water-soluble polymer nanoparticles(NPs) of about 42 nm formed by multivalent host–guest interactions between PCD and PAZO in aqueous solution were successfully obtained later. The structure of PAZO and PCD were characterized by lH NMR and GPC,the self-assembly behaviors of PAZO and PCD were determined by TEM.(3) The application of controlled drug release system of polymer nanoparticles(NPs) formed by multivalent host–guest interactions between PCD and PAZO: Chemiluminescent substance(oxalate) and fluorescent drugs(camptothecin) were wrapped inside the above mentioned nanoparticles by ultrasonic method forming CPPO and CPT contained nanoparticles(CPPO@CPT@NPs). The performance of CPPO@CPT@NPs were confirmed by DLS and TEM. After the addition of H2O2, the drug will be released triggered by fluorescence of chemiluminescence system of CPPO, CPT, H2O2 via azobenzene isomerization. The low cytotoxicity of the polymer nanoparticles without CPT was demonstrated by MTT assay. CPPO@CPT@NPs exhibits good response to H2O2 and can kill cancer cells efficiently. All these experiments shows that our materials have good potentials in controlled release drug system for cancer therapy.