Siddiqui Imtiaz A, Adhami Vaqar M, Bharali Dhruba J, Hafeez Bilal B, Asim Mohammad, Khwaja Sabih I, Ahmad Nihal, Cui Huadong, Mousa Shaker A, Mukhtar Hasan
Department of Dermatology, University of Wisconsin, Madison, Wisconsin 53706, USA.
Cancer Res. 2009 Mar 1;69(5):1712-6. doi: 10.1158/0008-5472.CAN-08-3978. Epub 2009 Feb 17.
Chemoprevention, especially through the use of naturally occurring phytochemicals capable of impeding the process of one or more steps of carcinogenesis process, is a promising approach for cancer management. Despite promising results in preclinical settings, its applicability to humans has met with limited success largely due to inefficient systemic delivery and bioavailability of promising chemopreventive agents. Here, we introduce the concept of nanochemoprevention, which uses nanotechnology for enhancing the outcome of chemoprevention. We encapsulated green tea polyphenol epigallocatechin-3-gallate (EGCG) in polylactic acid-polyethylene glycol nanoparticles and observed that encapsulated EGCG retains its biological effectiveness with over 10-fold dose advantage for exerting its proapoptotic and angiogenesis inhibitory effects, critically important determinants of chemopreventive effects of EGCG in both in vitro and in vivo systems. Thus, this study could serve as a basis for the use of nanoparticle-mediated delivery to enhance bioavailability and limit any unwanted toxicity of chemopreventive agents, such as EGCG.
化学预防,尤其是通过使用能够阻碍致癌过程中一个或多个步骤的天然植物化学物质进行的化学预防,是一种很有前景的癌症管理方法。尽管在临床前研究中取得了令人鼓舞的结果,但由于有前景的化学预防剂的全身递送效率低下和生物利用度有限,其在人类中的应用取得的成功有限。在此,我们引入了纳米化学预防的概念,即利用纳米技术提高化学预防的效果。我们将绿茶多酚表没食子儿茶素-3-没食子酸酯(EGCG)包裹在聚乳酸-聚乙二醇纳米颗粒中,观察到包裹后的EGCG保留了其生物学有效性,在发挥促凋亡和血管生成抑制作用方面具有超过10倍的剂量优势,这是EGCG在体外和体内系统中化学预防作用的关键重要决定因素。因此,本研究可为使用纳米颗粒介导的递送提高生物利用度并限制化学预防剂(如EGCG)的任何不良毒性提供依据。