Smart Polymeric Nanoparticles

Smart nanoscale drug delivery systems combine the advantage of the small size, to achieve passive targeting capacity and enhanced cell internalization, with the ability to undergo morphological or chemical changes in response to the target-site microenvironment, leading to accelerated release in the disease milieu. Such systems are designed to respond to a variety of different internal stimuli that characterize diseased tissues, the most common of which are pH, reductive environment, temperature, and enzyme concentration. For instance, tumor pH is substantially lower than normal tissue pH, and the concentration of certain enzymes, such as matrix metalloproteases, is increased to sustain tumor growth. Moreover, the high rate of cell proliferation and the lack of an efficient circulation system make the microenvironment highly reductive. All of these features can be exploited to maximize drug delivery at the target site, through the design of delivery systems that accelerate payload release under the specific target-site conditions. This chapter reviews the most common stimuli-sensitive polymer drug delivery systems, with a specific focus on tumor milieu-responsive nanoparticles.