Synthesis And Cancer Chemopreventive Activities Of Curcumin Nanocomposites

In order to reduce the incidence and mortality of cancer,cancer chemoprevention which can reverse or delay the progression of carcinogenesis is an alternative and cost-effective strategy.Recently,purified or extracted phytochemicals have become the focus of cancer chemoprevention research because of their routine use in the food supply,their diverse and potent anticarcinogenesis molecular mechanisms and their acceptability to healthy populations as food-based chemopreventive agents that are “healthy” and potent with a large therapeutic index.Among the large numbers of phytochemicals being studied as chemopreventive agents,curcuminoids stand out in their anticarcinogenesis potency,its multiplicity of molecular targets and favorable therapeutic index.However,its in vitro and in vivo effects have not been able to be translated to clinical use due to the poor water solubility,low stability and inefficient bioavailability.Therefore,in this paper,three kinds of curcumin nanocomposites with high drug loading,high stability in physiological conditions,low toxicity,good biocompatibility and stimulation-responsive properties have been synthesized to improve the water solubility and stability of curcumin and enhance its bioactivity and bioavailability.Moreover,the in vitro and in vivo antioxidant and anticancer activities of these curcumin nanocomposites have been studied.The methods and results are as following:(1)Synthesis of curcumin-polyvinylpyrrolidone nanocapsules and their in vitro cancer chemopreventive activitiesCurcumin-polyvinylpyrrolidone nanocapsules were prepared by simple esterification and solvent precipitation.Results of the characterization with electron microscopy and spectrometers showed that curcumin-polyvinylpyrrolidone nanocapsules were spherical particles with an average diameter of ~52 nm and their drug loading capability and drug loading efficiency were 89.54 ± 3.65% and 96.77 ± 1.02%,respectively.They were very stable in phosphate buffer solution and they can effectively and continuously release the loaded curcumin molecules.Results of the measurements of their free radical scavenging activities and cytotoxicity showed that these curcumin-polyvinylpyrrolidone nanocapsules had high scavenging activities to diphenyl keto acyl radicals and hydroxyl radicals,and could inhibit the proliferation of Hep G2 cells by inducing apoptosis.(2)Synthesis of curcumin-selenium nanoparticles and their in vitro cancer chemopreventive activitiesCurcumin-selenium nanoparticles were prepared by a p H-assisted method.Results of the characterization with electron microscopy and spectrometers showed that curcumin-selenium nanoparticles were spherical particles with an average diameter of ~125 nm.Curcumin molecules were firmly bound to the surface of selenium nanoparticles by Se-O bond,which enhanced the stability of curcumin and selenium nanoparticles in phosphate buffer solution and serum-free medium.The results of free radical scavenging test showed that the free radical scavenging activities of curcumin-selenium nanoparticles was mainly due to the free radical scavenging activities of curcumin molecules when their concentrations were low and selenium nanoparticles did not show obvious free radical scavenging activities.At high concentrations,both selenium nanoparticles and curcumin had significant free radical scavenging activities and they exhibit synergistic effects.Moreover,curcumin-selenium nanoparticles could promote the activation of caspase-3 and caspase-9 and induced the production of intracellular reactive oxygen species(ROS)in Hep G2 cells.Thus,they effectively inhibit the proliferation of Hep G2 cells by inducing apoptosis.(3)Synthesis of curcumin-zeolite imidazole framework-hyaluronic acid nanoparticles and their in vitro cancer chemopreventive activitiesCurcumin-zeolite imidazole framework nanoparticles were prepared by a "one pot" method and curcumin-zeolite imidazole framework-hyaluronic acid nanoparticles were obtained by surface modification of curcumin-zeolite imidazole framework nanoparticles with hyaluronic acid.Results of the characterization with electron microscopy and spectrometers showed that curcumin-zeolite imidazole framework-hyaluronic acid nanoparticles were truncated cubes with an average diameter of ~130 nm and their drug loading capability and drug loading efficiency were 10.1%and 88.2%,respectively.The size and shapes of zeolite imidazole framework nanoparticles were successfully changed by changing the concentration of curcumin in the reaction system.Drug release test showed that curcumin-zeolite imidazole framework-hyaluronic acid nanoparticles had a p H-responsive property and the release rate of curcumin was significantly accelerated in acidic phosphate buffer solutions.Cytotoxicity test showed that curcumin-zeolite imidazole framework-hyaluronic acid nanoparticles were able to selectively deliver high doses of curcumin to MCF-7 cells and they could induce apoptosis of MCF-7 cells through blocking their cell cycles in S Phase and G2/M phase and increasing the production of intracellular ROS,and ultimately inhibited the proliferation of MCF-7 cell.(4)The in vivo cancer chemopreventive activities of curcumin-zeolite imidazole framework-hyaluronic acid nanoparticlesThe in vivo cancer chemopreventive activities of curcumin-zeolite imidazole framework-hyaluronic acid nanoparticles were studied in a 4T1 lung metastatic mouse model.Cytotoxicity test showed that curcumin-zeolite imidazole framework-hyaluronic acid nanoparticles could inhibit the proliferation of 4T1 mouse breast cancer cells by inducing apoptosis and the in vitro metastatic and invasive abilities of 4T1 cells were significantly reduced after the treatment with curcumin-zeolite imidazole skeleton-hyaluronic acid nanoparticles.Results of 4T1 lung metastatic mouse model test showed that curcumin-zeolite imidazole framework-hyaluronic acid nanoparticles could effectively deliver curcumin to the tumor site during in vivo circulation and inhibit tumor growth and transfer by inducing tumor cell apoptosis.