Page - (000362) - in Biomedical Chemistry: Current Trends and Developments

potential factors that may provide an opportunity to selectively deliver drugs efficiently in the tumor sites via an enzyme-triggered mechanism. One of the most popular approaches is based on the altered expression of matrix metalloproteinases (MMPs), since in the MMP family, the up- regulation of MMP2 and MMP9 is generally recognized as involved in the invasion, progression and metastasis of most human tumors (Mansour, 2003). Zhu developed a multifunctional complex drug delivery system that has prolonged blood circulation time, targets specifically to tumor cells, responds to the up-regulated matrix metalloprotease 2 (MMP2) in the tumor microenvironment and has enhanced intracellular delivery by coupling specific moieties to the surface of a liposomal nanovector (Zhu, 2012). They were able to show a significant increase in the tumor targetability, as well as tumor cell internalization of the nanocarrier, and thus, this approach may be useful for selective drug delivery of cargos in the tumor sites. Other up-regulated enzymes, namely cancer-associated enzymes, have been utilized for the same purpose in liposomal formulations, yielding positive results of fast release kinetics in the specific tumor site (Basel, 2011). 3.5.2.3 Combination Therapy Cancer is a multifactorial disease and often the clinical treatment requires the administration of more than one drug molecule in order to achieve successful therapeutic outcomes. In addition, cancer cells frequently become multidrug resistant, by developing defense mechanisms against the therapeutic approach, like expression of different receptors/target proteins, self-repairing mechanisms or/and alterations in their own metabolism, evolving towards a weaker response to the treatment (Holohan, 2013). The combination of different therapeutics can lead to reduced drug resistance and synergize the therapeutic effect of different active substances, and thus, a dual positive outcome on the improvement of therapeutic effectiveness and decrease of deleterious effects (Hu, 2010). Despite the positive advantages of the association of multidrugs in a delivery system, it is rather challenging to efficiently co-load different drug molecules, often with distinct physicochemical properties, in the same ordinary