Chemoprevention, especially through the use of naturally occurring phytochemicals capable of impeding the process of carcinogenesis at one or more steps, is an ideal approach for cancer management. Despite accomplished outcomes in preclinical settings, its applicability to humans has met with limited success for many reasons including inefficient systemic delivery and bioavailability of promising chemopreventive agents. We have recently introduced a novel concept of "nanochemoprevention" that utilizes nanotechnology for enhancing the outcome of chemoprevention (Cancer Res 69, 1712-1716, 2009). To establish the usefulness of nanochemoprevention in cancer management, we studied the efficacy of a well identified chemopreventive agent epigallocatechin-3-gallate (EGCG) encapsulated in polylactic acid (PLA) and polyethylene glycol (PEG) nanoparticles (hereafter referred to as nano-EGCG) in preclinical settings. Nano-EGCG was found to retain its biological effectiveness, with over 10-fold dose advantage compared to nonencapsulated EGCG for exerting its cell growth inhibition, proapoptotic, and angiogenic inhibitory effects. Nano-EGCG was also observed to be effective in inhibiting tumor cell growth in athymic nude mice, with over 10-fold dose advantage compared to nonencapsulated EGCG. The rate of degradation of nonencapsulated EGCG was rapid, with a complete degradation within 4 h, whereas nano-EGCG had a significantly longer half-life. This study provides a foundation for the use of nanoparticle-mediated delivery of natural products to enhance the bioavailability of active agents for their enhanced effective and chemopreventive potential. In doing this, it is hoped that perceived toxicity concerns associated with prolonged use of agents could also be minimized. Oral consumption is the most desirable and acceptable form of delivery of chemopreventive agents. One disadvantage of using PLA-PEG nanoparticles is its unstable nature in acidic environment; and therefore, it is not recommended for oral consumption. To overcome this obstacle, it will be important to develop nanoparticles encapsulating phytochemicals that are suitable for oral consumption.