Food Grade Nanodelivery Systems of Phytochemicals for Prevention of Colorectal Cancer

 性状（申请人提供）：许多食源性植物化学物质具有很强的抗癌活性，可用作安全的抗癌治疗或预防剂。然而，许多植物化学物质是亲脂性的并且不稳定。虽然它们具有很强的抗氧化活性，并在体外有效地抑制癌细胞的增殖，但体内抗癌活性通常要低得多。此外，尽管研究了许多植物化学物质的递送系统，但由于合成包封材料的使用、有机溶剂的使用和工艺的可扩展性的限制，很少有实用的。该提案的目标是制造基于食品生物聚合物的亲脂性植物化学物质的纳米递送系统，用于预防癌症的功能性食品。在正在进行的实验中，将姜黄素溶解在pH 12.0的乳蛋白（酪蛋白酸钠）溶液中，随后使用磁力搅拌板中和，有效地将姜黄素包封为纳米颗粒。这些处理不会引起姜黄素的降解，并且纳米胶囊化的姜黄素对HCT-116细胞的抗增殖活性比预溶解在二甲基亚砜中的姜黄素有很大提高。初步数据表明，低成本，食品级纳米递送系统的创新，一些亲脂性植物化学品制造容易扩展的过程，而不需要专门的设备，有机溶剂，和合成/改性材料。基于使用姜黄素的初步发现，我们假设亲脂性植物化学物质的体内抗癌活性可以通过使用上述低成本、低能量和无有机溶剂的方法在食品生物聚合物中进行纳米封装来增强。该假设将在两个具体目标中进行测试：1）将使用酪蛋白酸钠和两种低粘度表面活性多糖（阿拉伯树胶和可溶性大豆多糖）作为代表性的可消化和不可消化的食物生物聚合物来研究纳米包封亲脂性植物化学物质的条件。[酪蛋白纳米胶囊将被封装在壳聚糖/果胶酸钙复合微粒中，用于在结肠中选择性释放。]姜黄素和芹菜素将被用作两个模型亲脂性植物化学物质。纳米颗粒的物理化学性质，纳米封装相关的性质，以及纳米封装的姜黄素和芹菜素的体外抗癌活性将使用各种技术进行表征。2)将通过体内模型证实纳米包封的芹菜素的体外抗癌活性。低成本、基于食品生物聚合物的纳米封装方法的创新解决了“范式转变方法制造用于癌症应用的纳米材料的优先事项，例如，改进对尺寸、形状、表面特性的控制，并降低制造成本”。安全和负担得起的输送系统使植物化学物质能够在功能性食品应用中用作癌症预防剂或癌症治疗剂。消除合成材料和有机溶剂可以减少免疫系统减弱的癌症患者的副作用和并发症。

 DESCRIPTION (provided by applicant): Many food-sourced phytochemicals have strong anticancer activities and can be used as safe anticancer treatment or prevention agents. Many phytochemicals however are lipophilic and are unstable. Although they have strong antioxidant activities and effectively inhibit the proliferation of cancer cells in vitro, the in vivo anticancr activities are typically much lower. Furthermore, despite many delivery systems studied for phytochemicals, few are practical due to limitations in the use of synthetic encapsulation materials, the use of organic solvents and the scalability of processes. The goal of this proposal is to fabricate nanodelivery systems of lipophilic phytochemicals based on food biopolymers for use of functional foods in cancer prevention. In ongoing experiments, dissolving curcumin in a pH 12.0 dairy protein (sodium caseinate) solution and subsequent neutralization using a magnetic stir plate effectively encapsulated curcumin as nanoparticles. The treatments did not cause the degradation of curcumin, and the nanoencapsulated curcumin showed much improved anti-proliferation activity against HCT-116 cells than curcumin pre-dissolved in dimethylsulfoxide. The preliminary data suggest the innovation of low-cost, food grade nanodelivery systems for some lipophilic phytochemicals fabricated with easily scalable processes without the need of specialized equipment, organic solvent, and synthesized/modified materials. Based on the preliminary findings using curcumin, we hypothesize that in vivo anticancer activity of lipophilic phytochemicals can be enhanced by nanoencapsulation in food biopolymers using the above low-cost, low- energy, and organic solvent-free processes. The hypothesis will be tested in two specific aims: 1) conditions of nano-encapsulating lipophilic phytochemicals will be studied using sodium caseinate and two low-viscosity surface-active polysaccharides (gum arabic and soluble soybean polysaccharide) as representative digestible and indigestible food biopolymers. [Casein nanocapsules will be encapsulated in chitosan/calcium pectinate composite microparticles for selective release in the colon.] Curcumin and apigenin will be used as two model lipophilic phytochemicals. Physicochemical properties of nanoparticles, properties related to nanoencapsulation, and in vitro anticancer activities of nanoencapsulated curcumin and apigenin will be characterized using various techniques. 2) in vitro anticancer activities of nano-encapsulated apigenin will be confirmed by in vivo models. The innovation of low-cost, food biopolymer-based nanoencapsulation method addresses the priority of "paradigm-shifting approaches to nanomaterials fabrication for cancer applications that could lead, e.g., to improved control of size, shape, surface characteristics, and lower fabrication costs" in the previous RFA PA-11- 149. The safe and affordable delivery systems enable the use of phytochemicals as cancer prevention agents in functional foods applications or as cancer curing agents. The elimination of synthetic materials and organic solvents can reduce the side effects and complications for cancer patients with weakened immune systems.