Characterizing lipid nanocarriers (LNCs) for targeting intracellular delivery of siRNA

Gene therapy by RNA interference is rapidly developing as a personal field of cancer treatment. Small interfering RNA (siRNA) plays a key role, enabling the targeting of disease-causing proteins. The successful application of siRNA relies heavily on efficient delivery systems. Lipid nanocarriers (LNCs) are used as drug delivery systems. However, tissue-specific targeting remains a key challenge to overcome. In this regard, we aim to design T7 peptide-functionalized liposomes, known for their ability to bind to the human transferrin receptor (hTfR), highly expressed on both the blood-brain barrier and blood–tumor barrier for glioma. A modified T7 peptide was synthesized and the highly selective thiol-maleimide reaction was chosen for further functionalization to DOPE-PEG2000-Mal. DOPE-PEG2000-Mal-T7 will be used as an LNCs substituent, with DPPC, DOTAP and cholesterol. By SANS measurements, exploiting the contrast-matching technique by using hydrogenated and deuterated lipids as components of the LNCs, we aim to understand where DOPE-PEG2000-Mal-T7 is located and the interaction between LNCs and hTfR.