Biofunctionalization of liposomes for tumour-targeted drug delivery

PEG-coated long-circulating liposomes have been successfully used as drug carriers in the treatment of many cancers for which clinical studies have shown enhanced therapeutic activity of the drug compared with the free drug (e.g. the liposomal doxorubicin formulation, Caelyx®). These studies have demonstrated the accumulation within solid tumors via an enhanced permeation retention (EPR) effect due to the longer circulation time. While EPR works as an effective passive targeting strategy, it would be desired to actively target cancerous cells to deliver anti-neoplastic agents, thereby limiting off-target toxicity.

Previous work within our laboratories has involved the synthesis of a series of peptide-PEG-lipid molecules that can be formulated into liposomal systems for application to lung cancer cells. The proposed research project aims to optimise the design of multifunctional PEG-coated liposomes, which combine the cancer cell targeting capability of specific peptides ligands for receptors over-expressed on lung tumour cells with the membrane-permeating properties of cell penetrating peptides (CPPs). Nano- and micro-sized carriers such as nanoparticles and liposomes develop a corona of biomacromolecules once exposed to biological tissue fluids; this corona often hides the original surface targeting groups and shields their functionality. Thus, it becomes essential for a successful targeted delivery to make a systematic study of the properties of these protein-liposome complexes to guarantee the bioactivity of the surface functional groups when interacting with the living matter in presence of environment proteins.

This project will involve the characterization of a series of PEG-coated liposomes functionalized with different ratios of the targeting and cell-penetration moieties both in aqueous physiological buffer and in biological fluids (serum, lung fluid, etc.). This study will be made in parallel with an in vitro screening on different cell lines for evaluation of cellular uptake of the drug as a function of the different surface functionalizations.