AACR 2022 | Improving the efficacy of mApoE-targeted liposomes by MMP2-controlled drug release in GBM

Milena Mattioli, PhD student at Humanitas Research Hospital, Lombardy, Italy, discusses strategies to further develop glioblastoma (GBM) treatment specificity and efficacy for modified ApoE (mApoE) targeted liposomes by incorporating matrix metalloproteinase (MMP2) controlled drug release. Preliminary results have demonstrated that mApoE, through the engagement of low-density lipoprotein receptors (LDLR), promotes mApoE-targeted liposome transcytosis across the blood-brain barrier (BBB) and confers target specificity towards glioblastoma stem cells (GSC)s. Modified liposomes successfully delivered a cytotoxic payload of doxorubicin. Irradiation enhanced LDLR expression on both the BBB and GSCs, thus further promoting modified liposome diffusion and specificity resulting in a significant reduction of in vivo tumor growth due to GSC apoptosis. Future directions for this project consist of developing a double functionalized liposome with MMP2 and mApoE- targeting peptides carrying kinase inhibitors of the MEK-ERK pathway to be evaluated for their anti-GSC activity in a patient derived GBM model. This interview took place at the American Association for Cancer Research Annual Meeting in New Orleans, LA.