Theranostic nanoplatform for cholesterol-impaired diseases
Abstract
Wider research context / theoretical framework: Cholesterol plays a crucial role in major cardiovascular and neurodegenerative diseases, including some rare genetic disorders showing altered cholesterol metabolism such as Niemann-Pick Type C. Cyclodextrins (CDs) have shown promising therapeutic efficacy based on their capacity to sequester and mobilise cholesterol. However, the administration of monomeric CDs suffers from several drawbacks due to their lack of specificity and poor pharmacokinetics. Hypotheses / research questions / objectives: The functionalisation of CDs onto SPIONs could represent an attractive theranostic platform to enhance the delivery of the cholesterol-mopping macrocycle in order to provide improved therapy for neurodegenerative disorders. We hypothesise that, through a process of receptor-mediated accumulation, CD-based, pH-responsive superparamagnetic iron oxide nanoparticles (SPIONs) will release CDs specifically into the lysosome where the cholesterol-mopping activity is most required. Approach / methods: Monodisperse biocompatible SPIONs will be modified with dimercaptosuccinic acid for lysosomal targeting and through pH-cleavable chemistry with CDs. The former will ensure a high concentration of cholesterol at the site of the desired action; the latter will ensure the release of the therapeutic agent only at the site of action.
cyclodextrin cholesterol magnetic nanoparticle intracellular targeting lysosome
Publikationen
Mitarbeiter*innen
Erik Reimhult
Univ.Prof. Dr. Erik Reimhult
erik.reimhult@boku.ac.at
Tel: +43 1 47654-80211
Project Leader
01.09.2020 - 31.08.2022
Antonino Puglisi
Dr. Antonino Puglisi
antonino.puglisi@boku.ac.at
Project Staff
01.09.2020 - 31.08.2022