## 4 Potential Applications of Peptide-Synthetic Polymer Hybrids
### Self-Assembled Nanoparticles/Micelles for Drug/Enzyme/Gene Delivery  
Polymeric micelles as drug delivery systems (DDS) offer many advantages [91,92], the most important being: i) colloidal stability with low critical micellar concentration (CMC), ii) tunable sizes with narrow size distribution, iii) ability to preserve the activities of drugs during circulation in blood, iv) high physical loading efficiency of drugs, v) bioconjugation for active targeting to specific diseased cells, and vi) controllable release of drugs upon external stimuli and degradation. Due to their sizerange (_i.e._, 10-100 nm) they are sufficiently large to avoid renal excretion, yet small enough to bypass filtration by the spleen. However, the applicability of peptide/polymer hybrids in this field has been only weakly explored since conventional block polymers where used instead of them. However as it has been commented along this review, peptides possess numerous advantages for creating new and advanced systems. For example, it is possible to have an accurate triggering and control over the different type of substance delivery (e.g., drugs, enzymes, genes) by taking into account the stimuli responsive behavior that some peptide blocks display in solution. Some of the recent advances in this field have also been commented in _Section 2_[21, 22, 23, 26, 29, 30, 47, 49, 52, 53, 80]. [PERSON] _et al._[93] have proposed an interesting procedure to monitor in real time the cargo release from hybrid nanocapsules induced by enzyme cleavage. Thus, polyurea/peptide hybrid nanocapsules containing a water-soluble dye (_i.e._, sulforhodamine 101) efficiently encapsulated were studied. The peptide sequences were specially prepared in such a way that they contained several features: the recognition sequence (Gly-Phe-Phe, GFF) for a peptidase and a surrounding FRET (Forster resonance energy transfer) system, which was attached to \(\varepsilon\)-amino groups of lysine residues. Specifically, 7-methoxycoumarin-4-yl-acetic acid (Mca) was employed as the fluorophore and 2,4-dinitrophenyl (Dnp) as a suitable quencher. In this system, emission upon excitation of the donor (fluorophore) remains unimpaired as long as the distance to the acceptor (quencher) is significantly greater than the Forster radius (1-8 nm). Decrease of the distance between donor and acceptor will result in nonradiative energy transfer from the donor to the acceptor (quenching). In the intact peptide sequence, the mutual distance is below the Forster radius, and thus FRET, which is a common tool in the detection of enzymatic activity, is highly effective. Cleavage of the peptide sequence will lead to a fluorescence signal due to the increasing distance between donor and acceptor that can be detected _in situ_. **Scheme XIV. ** Cargo release from peptide-based hybrid nanocapsules induced by enzyme cleavage based on [93]. The cleavage of the peptide sequence by using trypsin as an enzymatic triggering was effectively monitored (by means of the FRET system), while the liberation of encapsulated dye was simultaneously detected by fluorescence recovery upon release to aqueous environment (Scheme XIV). The influence of the synthetic parameters on the size of the polymer chains, the morphology of the capsules and the encapsulation efficiency could be effectively studied by the given approach. Moreover, results clearly indicated that the fluorescence of the dye increased simultaneously to the Mca fluorescence only when the enzyme was added. Therefore, it was possible to infer that the dye was released from the capsules, and that its fluorescence was no longer quenched because of encapsulation. The proposed approach opens interesting perspectives for specific enzyme-triggered drug delivery using nanostructured materials. The same methodology was also used for studying hydrophobic crosslinked nanoparticles (_i.e._, 230 nm of diameter), based on peptide-functionalized polystyrene [94].