5-2.1.4.3. Polyphosphoester

Polyphosphoesters (PPE) are biocompatible and biodegradable, particularly those having a backbone analogous to nucleic acids and teichoic acids and used in several biomedical applications.They may result in extracellular persistent release of the DNA molecules thus enhancing the expression of transgene in the muscle as compared to naked DNA intake.
Several polyphosphoesters with positive charges both in the backbone and in the side chain can be used as non-viral gene carriers.
They can efficiently bind and protect DNA from nuclease degradation.
They exhibit a significantly lower cytotoxicity than Poly-L-Lysine or polyethylenimine both in vitro and in vivo.
It is a cell type dependent transfection method the efficiency of which can be enhanced using chloroquine.
The transfection using polyphosphoestersis found to be effective in many cell lines, with some of them comparable to Liposome-mediated transfection.

5-2.1.4.4. Dendrimers

Dendrimers are a new class of polymeric materials that are highly branched and monodisperse macromolecules. Due to their unique behaviour, they are suitable for a wide range of biomedical applications.
They have positively charged amino groups (termini) on their surface which interact with the negatively charged phosphate groups of the DNA molecule to form a DNA-dendrimer complex.
This DNA-dendrimer complex has an overall net positive charge and interacts with negatively charged surface molecules of the cell membrane thus allowing the entry of complex into the cell through non-specific endocytosis.
Once inside the cell, these complexes are then transported to the endosomes where these are protected from nuclease degradation by being highly condensed within the DNA-dendrimer complex.
The unprotonated amino groups on the dendrimers at neutral pH can become protonated in the acidic environment of the endosome leading to buffering of the endosome and thus inhibiting pH-dependent endosomal nucleases.

Figure 5-2.1.4.4: Structure of a dendrimer.