Harnessing Lipid Nanoparticle Technology for Innovative Vaccine Delivery Solutions

Project description

Cancer remains one of the most significant health challenges globally, accounting for approximately 10 million deaths annually. It poses a substantial disease burden on healthcare systems and economies due to high treatment costs and lost productivity. Additionally, cancer significantly impacts the quality of life for patients and their families, necessitating the development of more effective and less toxic treatments to alleviate this widespread burden. Liposomes are spherical vesicles composed of lipid bilayers that encapsulate bioactive molecules, enhancing their stability, bioavailability, and targeted delivery to specific tissues or cells. This project aims to engineer liposome formulations to improve the efficacy and safety of antigenic cancer peptide vaccines by overcoming biological barriers. The properties of liposomes, such as size, surface properties, and composition, can be tailored depending on the additives used in their preparation. Furthermore, the active surface of liposomes allows for functionalization to modify surface properties and conjugate therapeutic molecules. Liposomes will be prepared using the thin-film hydration method followed by extrusion. Lipid components, such as phospholipids and cholesterol, will be dissolved in an organic solvent, followed by solvent evaporation to form a thin lipid film. This film will be hydrated with an aqueous solution containing antigenic peptides to form multilamellar vesicles, which will then be extruded through polycarbonate membranes to obtain unilamellar liposomes of the desired size. Antigenic peptides will be synthesized using solid phase peptide synthesis which involves the stepwise addition of protected amino acids to a growing peptide chain anchored to a solid resin. After assembly, the peptides will be cleaved from the resin and purified using high-performance liquid chromatography to ensure high purity and yield. The efficacy of the liposome-encapsulated antigenic peptides will be assessed in C57BL/6 mice vaccine challenge studies. Mice will be immunized with the liposomal vaccine and challenged with a syngeneic cancer cell line to establish cancer models. Cancer growth will be monitored, and immune responses will be evaluated by analysing tumour-infiltrating lymphocytes, cytokine profiles, and overall survival rates. Additionally, toxicity studies will be conducted to assess potential adverse effects. By optimising these formulations, the project aims to enhance immune responses against cancer cells while minimising adverse effects. This research has high translational potential, providing a platform for developing other therapies and advancing cancer treatment.

Outcomes

The student will obtain training in antigenic peptide synthesis, purification, and characterisation; liposome and nanoparticle formulations; in vitro and in vivo vaccinology; cancer immunotherapy; and structure-activity study design. The student will obtain translatable skills in project leadership, time management, critical thinking and problem solving. These skills will train the student in developing new formulations needed for cancer therapy. The outcomes of this project are commercially significant and would lead to project outcomes which can be employed in developing combinatorial therapy, not only for cancer, but applied more broadly to other important human diseases.

Essential capabilities

Training in sciences – especially biological and chemical.

Desireable capabilities

Experience in relevant areas e.g. cancer research, drug formulation, biotechnology, chemistry, materials science. Lab experience would be favourable.

Expected qualifications (Course/Degrees etc.)

Science, Biotechnology, Engineering, or Pharmacy/Pharmaceutical Sciences qualifications for PhD study.

Additional information for applicants

note: i-students must have own scholarship to apply (CSIR, UCG-NET, etc)