Page - (000357) - in Biomedical Chemistry: Current Trends and Developments

Figure 3.5.2: Chemical structure of the triblock copolymer PEG-b-PCL-b-poly (2- aminoethylethylene phosphate) and schematic illustration of the micellar nanoparticle formation and loading of paclitaxel and siRNA. Reprinted with permission from (Sun, 2011). Nowadays, the most advanced systems are not so simple and combine a series of different functionalities that render tunable release of cargos, triggered release properties, selectivity, and the possibility of tracking the nanocarriers by imaging and even combined therapy of several active substances. Such systems are further described in the sections below. 3.5.2.2 Stimuli-responsive Controlled Drug Delivery Systems Nanoparticulate systems have been widely used for drug delivery when combined to molecules that have the particularity to react to certain physiological or pathological changes in the surrounding environment (Jhaveri, 2014). This is an approach that offers additional opportunities to enhance tumor accumulation of drugs that are administered systemically, increasing the chances of a more successful therapeutic outcome when treating solid tumors and avoiding unnecessary drug distribution in healthy tissues, thus minimizing the toxic side effects of the drugs (Nakayama, 2014). Different strategies have been investigated and nowadays there are different nanosized platforms capable of responding to different stimuli (Fig. 3.5.3) that can be tumor extrinsic, such as application of light, magnetic field, heat or ultrasounds; or intrinsic to the tumor-like pH, reductive potential changes or up- regulation of proteins or enzyme expression (MacEwan, 2010; Nakayama, 2014; Yang, 2013; Zhu, 2013). In this section we will explain different tumor-intrinsic stimuli-responsive strategies recently applied in the research field.