Enzyme-responsive nanocarriers

Smart polymeric carriers for drug delivery enzyme-responsive nanocarriers... 

In the rest of this section, key examples of enzyme-responsive nanocarriers will be discussed, as well as their applications for enzyme-mediated drug... 

Harnoy AJ, Rosenbaum 1, Tirosh E, Ebenstein Y, Shaharabani R, Beck R, Amir RJ. Enzyme-responsive amphiphilic PEG-dendron hybrids and their assembly into smart micellar nanocarriers. J Am Chem Soc 2014 136(21) 7531. ... 

To date, two main approaches have been adopted for developing enzyme-responsive materials. In the first and most common approach, the nanocarrier itself is sensitive to enzymatic transformation. This is achieved by the use of either an enzymatically degradable polymer or enzymatically sensitive linkers between the drug and the polymer. 

The second approach is based on the surface modification of the nanocarriers with molecules that confer enzymatically triggered changes of the physical properties of the carrier solution. This approach is extremely versatile and has been mainly used in developing inorganic enzyme-responsive nanoparticles (Medintz et al, 2005 Stevens et al, 2004 Zelzer and Ulijn, 2010) for which use as DDS has not been so fully developed because of toxicological concerns. It will not therefore be discussed in this chapter. For further information the reader is referred to some excellent recent literature (de la Rica et al, 2012 Ghadiali and Stevens, 2008 Hu et al, 2012 Nie era/., 2009). 

In summary, very important progress has been made with regard to redox-responsive polymeric nanocarriers during the past decade and it seems that they will soon be among the most promising stimuli-responsive systems (which are currently the pH- and enzyme-responsive systems) when directed to peptide, protein or gene delivery. 

As mentioned above, tumor-associated MMPs have been an interesting enzyme species for designing triggered and responsive nanocarrier systems. A bio-responsive cisplatin (CDDP] delivery system with a self-assembling peptide amphiphile (PA] constituting a cell-adhesive matrix metalloproteinase-2 (MMP-2]-sensitive... 

An emerging area of research in stimuli-responsive polymeric nanocarriers is related to nanomaterials that experience macroscopic property changes mediated by the catalytic activity of enzymes. The importance of this field is evident by the large number of recent publications related to it (de la Rica et al., 2012 Fleige et al., 2012 Hu et al., 2012). 

Overall, stimuli-responsive, smart nanocarriers are a very important emerging area of drug delivery. Those most commonly studied involve endogenous stimuli (pH, enzymes and redox potential), which take advantage of specific conditions that exist intraceUularly or in the microenvironment of the disease site, enabling selective drug release. 

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