Enhancing Chemotherapy by RNA Interference

A single cell mutation is what it takes to initiate cancerous growth. Yet, tumor mass does not develop in a matter of days. Cancer cells develops the ability to escape from the homeostatic control system due to the accumulation of mutation, leading to selective genetic and epigenetic changes that enhance the thriving, proliferation, and avoidance of apoptosis pathways. Chemotherapy for the treatment of cancer was introduced in clinic more than five decades ago and remains the first choice for physicians treating localized primary tumors. Nevertheless, using it for treatment of other epithelial tumors such as breast, colon, and lung cancer is not plausible. Theoretically, the ideal scenario is for a chemotherapeutic drug to target neoplastic cells specifically, thus reducing tumor burden without causing side effects or collateral damage to normal cells. In reality, chemotherapeutics is hampered by the rapid development of drug resistance, poor pharmacokinetics of chemotherapeutic agents, and the systemic toxicity attribute to lack of specificity [1]. Since Matsumura and Maeda discovered the enhanced permeation and retention (EPR) effect, the development of nanoparticles has led a revolution in anticancer drug delivery systems [2]. In general, the design of nanoparticle-based chemotherapeutic is usually with a chemotherapeutic agent encapsulated in, complexed with or attached to, a well-designed nanoparticle [3]. The superiority of nanoparticles over conventional chemotherapeutics includes enhanced pharmacokinetics ability, augmented tumor accumulation attribute to the EPR effect, and increased tumor targeting due to the tumor-specific targeting moiety (i.e., antibody, peptide, small molecule) of nanoparticles. Nanoparticles usually range from <10 nm to approximately 500 nm and thus cannot extravasate from normal vasculatures. As a result, nanoparticle retention in normal tissues, such as skin, spleen, muscle, lung, heart and kidney, is lower compared with chemotherapeutics. Moreover, multiple therapeutic or diagnostic reagents could be incorporated into some nanoparticles to achieve synergistic therapy as well as real-time monitoring [4]. Successful clinical application of ABSTRACT