Quaternized Starch Modified by Cetuximab as Nano Carrier for siRNA Targeted Delivery for Head and Neck Cancer

The scientific progress in cancer therapy, which is based on understanding molecular process inside cancerous cells, had brought to the development of biological medications that target a specific protein or a specific process inside cancer cells. One of those drugs is the synthetic antibody, cetuximab (Erbitux), who belongs to the epidermal growth factor receptor (EGFR) blockers. This antibody is highly specific to cells expressing EGFR, overexpressed in several cancers including head and neck cancer. The antibody-receptor binding delays the receptor’s activation and subsequent signal-transduction events leading to cell proliferation. Unfortunately, cancer cells become refractory to antibody and retune to uncontrolled proliferation. Another approach, currently investigated, to treat cancer and genetic diseases is delivery of small interfering RNA (siRNA) to downregulate proteins that are involved with the cancer cascade. The main goal of this research is to exploit the specific features of the antibody to deliver siRNA in a specific route cancer cells overexpressing. This delivery system is based on quaternized starch (Q-starch) as a carrier for siRNA which is biocompatible and biodegradable, and therefore an attractive biopolymer for therapeutic purposes. In one hand, Q-starch assists siRNA to overcome biological barriers in its delivery pathway, and on the other hand, serves as a linker to cetuximab to improve specificity to cancer cells.

So far, modified starch was successfully obtained by substitution with quaternary reagent, providing Q-starch the cationic property. The attachment of cetuximab antibody to Q-starch via PEGylation was also successful. The carrier was able to interact with negative siRNA to form suitable complexes. The physical properties of the complexes are characterized by several methods as dynamic light scattering, zeta potential, and cryogenic transmitted electron microscopy. These properties are important for successful siRNA delivery and gene silencing, which will be examined in the next part of this study.