Multifunctional Polymeric Nanosystems for Tumor-Targeted Delivery (original) (raw)

Cancer is the second leading cause of morbidity and mortality in the United States, with occurrences portraying an upward trend for the future. In 2007, approximately 10 million cases of cancer will occur globally, with a total of around 1.5 million new cancer cases and over 560,000 deaths expected in the United States (U.S. National Institute of Health, 2006). Strikingly, remarkable advances in diagnosis and therapy of cancer have been made over the past few decades resulting from significant advances in fundamental cancer biology. What lacks in this case is clinical translation of these advances into effective therapies. A major hurdle in cancer diagnosis and therapy is the targeted and efficacious delivery of agents to the tumor site, while avoiding adverse damage resulting from systemic administration. While systemic drug delivery already hinges largely on physicochemical properties of the drug, such as size, diffusivity, and plasma protein binding affinity, tumors possess a dense, heterogeneous vasculature and an outward net convective flow that act as hurdles to efficient drug deposition at the target site (Jang et al., 2003). Nanocarriermediated delivery has emerged as a successful strategy to enhance delivery of therapeutics and imaging agents to tumors, thereby increasing the potential for diagnosis at an earlier stage or for therapeutic success (or both). Based on the initial observation by Maeda and Matsumura that tumors possess a fenestrated vasculature, with pores on average ranging between 200 and 800 nm, and a lack of lymphatic drainage, together termed the enhanced permeability and retention (EPR) effect, it was found that colloidal carriers in the nanometer size range could target tumors passively, by specific extravasation through these fenestrations, and are retained at the site for prolonged time because of lack of lymphatic drainage (Matsumura and Meada, 1986). This physiological advantage has been used successfully to enhance delivery of diagnostic and therapeutic agents, leading to the U.S. Food and Drug Administration (FDA) approval of nanoparticle formulations such as Feridex® for diagnostic applications and Doxil® and Abraxane® for cancer therapy (U.S. Food and Drug Administration, 2006).