*5.1.3 Genes*

The new systems for oncotherapy under development focus on selectivity so that they reach tumor cells without affecting the healthy ones. One strategy is to incorporate genes in non-viral carriers via surface modification to increase selectivity and affinity for the target cell's receptors. Nanocapsules with ter-polymers, to deliver DNA into tumoral cells, were developed. The surface of the nanocapsules was activated with folic acid so as to enable interaction with the folate receptors overexpressed [108]. Folate-decorated reductive-responsive carboxymethylcellulose-based nanocapsules were also prepared for targeted delivery and controlled release of hydrophobic drugs. In this case, the shell was cross-linked by disulfide bonds formed from hydrosulfuryl groups on the thiolated carboxymethylcellulose. These systems could become potential hydrophobic drug carriers for cancer therapy [109]. In addition, the first experiment with DNA-derived nanocapsules designed to reach podocytes, which damage plays a central role in the pathogenesis of idiopathic nephrotic syndrome, as well as in the progression of many chronic glomerular diseases, has been developed. These nanocapsules were composed of chitosan and plasmids, and their size, the number of plasmid layers, and the presence of the solid template were investigated in particular as the main parameters impacting the biological assay [110]. Besides, nanocapsules obtained from chitosan with hyaluronic acid for genes delivery into the lung epithelium were described. The nanocapsules were introduced in mannitol microspheres to facilitate administration in the lungs. This was seen as a good strategy for the delivery of genetic material into the lung [111]. In a different study, spherical nanocapsules were obtained from chitosan and loaded with capsaicin for cystic fibrosis treatment, and wtCFTR-mRNA was linked to the surface. They happened to be highly stable in the cell culture transfection medium [112]. Also, polyarginine was encapsulated in glyceryl-monooleate-based liquid droplets together with the immunomodulator chemokine CCL2 and two RNAi sequences. It was concluded that polymeric shells confer multifunctionality to the nanocapsules due to their versatility, which permits control of the mechanism of the therapeutic action [107]. An analogous of the nucleotide GMP was encapsulated in lipid nanocapsules for the treatment of neurodegenerative retinal degenerations. The nanocapsules were prepared from Labrafac™ lipophile, Kolliphor®, and phospholipids, and remained stable for 6 days in phosphate buffer and in vitreous components, allowing for a sustained release [113].
