Matrix Metalloproteinase Triggered Liposomal Drug Release for Precision Cancer Therapy
Description: Liposome-based drug delivery systems (DDS) can improve the efficacy of chemotherapeutics and reduce their side effects. Liposomes accumulate in tumors as a result of the enhanced permeability and retention (EPR) effect. To provide a therapeutic effect the drugs must be released from the liposomes, which typically is a slow process that relies on passive diffusion. The slow release can result in drug concentrations outside the therapeutic window, reducing drug efficacy and increasing risks for development of drug resistance. In this project we will develop and explore a strategy for efficient and rapid liposomal drug release triggered by matrix metalloproteinases (MMPs). MMPs are significantly overexpressed in tumors and are involved in almost every hallmark of cancer, including tumor growth, tissue remodeling, inflammation, tissue invasion, and metastasis. We will develop a library of flexible and modular peptides that will be tethered to liposomal DDS and that will trigger membrane disruption only when proteolytically cleaved by specific MMPs. The peptides will, in addition to lipid bilayer anchoring moieties, contain a membrane active peptide, an MMP-recognition sequence and a peptide/polymer that prevent membrane disruption. When cleaved by an MMP, the latter will be excised, triggering membrane disruption and drug release. Targeting MMPs for triggered drug release is expected to facilitate development of more sophisticated, precise and effective cancer treatments.
Funder: Vetenskapsrådet
Amount: SEK 3,056,000
Funding type: research
Funder scheme: Project grant
Start date: 2018-01-01
End date: 2021-12-31
Investigator: Daniel Aili
Institution: Linköping University
Funded outputs count: 13
Funder award ID: 2017-04475
OpenAlex ID: G2532722037