The advent of nanotechnology has had a revolutionary impact on many aspects of 21st 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.
The size and morphology of chitosan-based nanoparticles encapsulating EGCG (CHI-EGCG-NPs) were examined by transmission electron microscopy (TEM). This technique allowed us to directly visualize the CHI-EGCG-NPs. It was found that the nanoparticles had a size of around 200 nm, which is further supported by what we observed earlier with our dynamic light scattering (DLS) data. Additionally, from the TEM picture, it is clear that the nanoparticles are spherical in shape. We also studied the release kinetics of EGCG from CHI-EGCG-NPs in simulated gastric juice and simulated intestinal fluid. It became clear from the data that the release of EGCG from these nanoparticles is very slow in acidic medium, even at 24 hrs only 10% of EGCG was released. On the other hand, release of intestinal fluid is much faster, and around 50% of EGCG was released in 24 hrs. We have earlier shown that treatment with CHI-EGCG-NPs (3 and 6 mg/kg body wt.) resulted in significant inhibition of tumor growth in athymic nude mice implanted with 22R 1 cells. Further extending this work, we report here that in tumor tissues of mice treated with both doses of CHI-EGCG-NPs as compared to group treated with EGCG and controls, there was significant (i) reduction in Ki-67 and proliferating cell nuclear antigen (PCNA) (ii) induction of poly (ADP-ribose) polymerases (PARP) cleavage, (iii) activation of caspases and, (iv) increase in the protein expression of Bax and decrease in Bcl2. Through this study, we propose a novel preventive and therapeutic modality using EGCG that addresses issues related to bioavailability, that is a major reason for its limited success in humans.