📋 Tender Overview
Engineering Lipid Nanoparticles To Target And Escape The Endosome, Deliver Their Cargo And Perform Better As Breast Cancer Therapies
There is a strong need for personalised genetic medicines for the treatment of advanced breast cancer. LNP-mRNA nanomedicines have already been proven as safe and cost effective in the SARS-CoV-2 vaccines. However, cancer treatments often require (i) repeat dosing (ii) controlled immune response (iii) adaptability to combat drug resistance. There are several LNP-RNA clinical cancer trials ongoing, many of which have reported challenges with toxicity, performance and specificity (off target effects). For an LNP-RNA cancer therapeutic to function, they need to localise in the correct organ, enter the cancer cells and escape the cellular (endosomal) processing pathway to release their RNA cargo. In current LNP-RNA formulations only a small fraction (<10 %) of LNPs successfully escape the endosome. However, these ‘null’ LNPs can still contribute to toxicity which places huge restrictions on their clinical application and performance. The aim of this proposal is to provide mechanistic insight into the endosomal escape of LNPs and use nanoscale engineering to target the endosome and improve LNP endosomal escape. This is particularly relevant in breast cancer as the majority of LNP systems are optimised for liver applications and designed to undergo fusion under ‘healthy’ endosomal conditions. In breast cancer, the composition (lipid, protein) and environment (pH) of the endosome differ significantly between healthy and cancer cells.
Funded Under
European Research Council (Erc)
Total Cost
€ 1 844 248,00
Eu Contribution
€ 1 844 248,00
Coordinated By
Kungliga Tekniska Hoegskolan
Sweden
