Surface Engineered Dendrimers in siRNA Delivery and Gene Silencing.

BACKGROUND: Therapeutic efficacy of dreadful diseases like cancer, HIV (Human Immunodeficiency Virus) can be enhanced by delivering molecules which regulate function at gene level rather than at receptor level. Silencing RNA is one such approach recently used to silence target gene expressed diseases; and thereby reduce target protein levels. Many of the non-viral vectors are proved to act as carriers for silencing RNA. Dendrimers being one of them have less size, low poly dispersibility index, water solubility, multivalence, and easy surface modification. Many such surface modifications have been carried out to improve the delivery potential of small interfering RNA (siRNA) modified dendrimers compared to simple plain dendrimers.

METHODS: Dendrimer was taken as a core whose surface was modified with fluorine, amino acids, phosphate, lipids, folate, specific antibody or RGD (Arg-Gly-Asp). The purpose of these modifications was to increase the therapeutic siRNA efficiency, lower the toxicity and improve the targeting potential of dendrimers.

RESULTS: Fluorinated dendrimers have highest electronegativity and highest siRNA loading capacity. Amino acid functionalized dendrimers are made up of endogenous amino acids which improve biocompatibility of dendrimer and endosomal escape. Carbosilane dendrimers increase the gene transfection ability of tissues to be treated. Phosphate dendrimers having hydrophobic backbone and hydrophilic surface increase the permeability towards targeted tissue. Lipid based dendrimer causes endosomal escape and improves the permeability of dendrimers. Targeting of specific tissues is achieved by coupling dendrimer with folate, RGD and specific antibody, thereby reducing off target effect.

CONCLUSION: Thus, surface modified dendrimers render a complete pack which offers increased siRNA loading, increased transfection and permeability, efficient targeting, endosomal escape and protecting siRNA from degradation by RNase and other such enzymes. The objective of this manuscript is to provide different approaches currently available for surface modifications of dendrimers and their overall effect on transfection ability of siRNA to target tissues.