Co-Delivery of Natural Compounds with Dual-Targeted Nanoparticle Delivery System for Improving Synergistic Therapy in Orthotopic Tumor Model.

Various natural compounds including epigallocatechin gallate (EGCG) and curcumin (CU) have potential in developing anticancer therapy. However, their clinical use is commonly limited by instability and low tissue distribution. EGCG and CU combined treatment can improve the efficacy with synergistic effects. To improve the synergistic effect and overcome the limitations of low tissue distribution, we applied a dual cancer-targeted nanoparticle system to co-deliver EGCG and CU. Nanoparticles were composed of hyaluronic acid, fucoidan, and poly(ethylene glycol)-gelatin to encapsulate EGCG and CU. Furthermore, a dual targeting system was established with hyaluronic acid and fucoidan, which were used as agents for targeting CD44 on prostate cancer cells and P-selectin in tumor vasculature, respectively. Their effect and efficacy were investigated in prostate cancer cells and a orthotopic prostate tumor model. The EGCG/CU-loaded nanoparticles bound to prostate cancer cells, which were uptaken more into cells, l...