Dual targeting strategy for breast cancer

Breast cancer (BC) is expected to be the second most commonly diagnosed cancer (after lung cancer) in Canada. Traditionally, multiple chemotherapeutics are given to BC patients with malignant tumours that cause side-effects and reduce patient compliance. We propose small interfering RNA (siRNA) technology that can deliver two different siRNA in BC cells. The proposed system is in early stages, but can improve patient survival while minimizing side effects of chemotherapeutic cocktails. The goal of this project is to develop smart, degradable and non-toxic peptide-based carriers for loading and delivery of two siRNA in breast tumours. The precision vectors designed will target breast cancer cells (BCCs) and will simultaneously inhibit different growth receptors present on their surface. The complete inhibition of growth promoting genes in BCCs would provide an effective treatment and will prevent growth and metastasis of breast tumours in vitro and in vivo. In this project, we aim to provide precise control on delivery of two siRNAs in breast tumours and will evaluate the potential of therapeutics to regress breat tumours and to prevent their metastasis. This will be achieved by the synthesis of peptide nanocarriers, followed by their covalent attachment with two different siRNAs at predetermined molar ratios. Peptide nucleotide conjugates will then be functionalized with antibodies for their selective targeting and for treatment of breast tumours. The peptide siRNA conjugates, capable of loading precise amounts of two siRNA drugs is the first example of targeted delivery of multiple siRNA in BCCs. In comparison to traditional approaches of combinatorial drug delivery, the development of degradable delivery carrier, with ability to deliver predetermined ratios of two drugs can significantly reduce the drug dosage and provide a safe alternative for breast cancer treatment. The data obtained from this study will be key importance for breast cancer research specifically and technology can be easily modified to incorporate patient tumor specific siRNA drugs.