Earlier we introduced the concept of ‘nanochemoprevention’ i.e. the use of nanotechnology to improve the outcome of cancer chemoprevention. Here, we extended our work and developed polymeric EGCG-encapsulated nanoparticles (NPs) targeted with small molecular entities, able to bind to prostate specific membrane antigen (PSMA), a transmembrane protein that is overexpressed in prostate cancer (PCa), and evaluated their efficacy in preclinical studies. First, we performed a molecular recognition of DCL- and AG-PEGylation on ligand binding on PSMA active site. Next, the biocompatible polymers PLGA-PEG-A were synthesized and used as base to conjugate DCL or AG to obtain the respective copolymers, needed for the preparation of targeted NPs. The resulting EGCG encapsulating NPs led to an enhanced anti-proliferative activity in PCa cell lines compared to the free EGCG. The behavior of EGCG encapsulated in NPs in modulating apoptosis and cell-cycle, was also determined. Then, in vivo experiments, in mouse xenograft model of prostatic tumor, using EGCG-loaded NPs, with a model of targeted nanosystems, were conducted. The obtained data supported our hypothesis of target-specific enhanced bioavailability and limited unwanted toxicity, thus leading to a significant potential for probable clinical outcome.

The advent of nanotechnology has had a revolutionary impact on many aspects of 21^st century life. Nanotechnology has provided an opportunity to explore new avenues that conventional technologies have been unable to make an impact on for diagnosis, prevention, and therapy of different diseases, and of cancer in particular. Entities in nanometer sizes are excellent platforms to incorporate various drugs or active materials that can be delivered effectively to the desired action site without compromising the activity of the incorporated drug or material. In particular, nanotechnology entities can be used to deliver conventional natural products that have poor solubility or a short half life. Conventional natural products used with entities in nanometer sizes enable us to solve many of the inherent problems (stability, solubility, toxicity) associated with natural products, and also provide a platform for targeted delivery to tumor sites. We recently introduced the novel concept of using nanotechnology for enhancing the outcome of chemoprevention, which we called ‘nanochemoprevention’. This idea was subsequently exploited by several laboratories worldwide and has now become an advancing field in chemoprevention research. This review examines some of the applications of nanotechnology for cancer prevention and therapy using natural products.

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.

Tea that contains many antioxidants is a pleasant and safe drink that is enjoyed by people across the globe. Tea leaves are manufactured as black, green, or oolong. Black tea represents ~78% of total consumed tea in the world, whereas green tea accounts for ~20% of tea consumed. The concept of "use of tea for promotion of human health and prevention and cure of diseases" has become a subject of intense research in the last decade. Diseases for which tea drinkers appear to have lower risk are simple infections, like bacterial and viral, to chronic debilitating diseases, including cancer, coronary heart disease, stroke, and osteoporosis. Initial work on green tea suggested that it possesses human health-promoting effects. In recent years, the research efforts have been expanded to black tea as well. Research conducted in recent years reveals that both black and green tea have very similar beneficial attributes in lowering the risk of many human diseases, including several types of cancer and heart diseases. For cancer prevention, evidence is so overwhelming that the Chemoprevention Branch of the National Cancer Institute has initiated a plan for developing tea compounds as cancer-chemopreventive agents in human trials. Thus, modern medical research is confirming the ancient wisdom that therapy of many diseases may reside in an inexpensive beverage in a "teapot."

Because prostate cancer has a long latency period and is typically diagnosed in elderly men, it represents an ideal candidate disease for chemoprevention. Therefore, even a modest delay achieved through intervention could have a significant impact on the outcome of this disease. Epidemiological and laboratory studies have provided convincing evidence that diet, genetic factors, and lifestyle are major causes of prostate cancer. Although surgery, radiotherapy, and hormone therapy are the most widely accepted curative options for a selected group of patients suffering from prostate cancer, the side effects of these treatments are many. In recent years, many dietary agents have been being described that show a wide range of chemopreventive effects in cell culture and selected animal model systems of prostate carcinogenesis. One such agent is the beverage tea, which, next to water, is the most popularly consumed beverage in the world. The epidemiological studies and recent data, amassed from various laborator...