Project description
Novel metal-organic nanocarriers for therapeutic brain delivery
Blood-brain barrier (BBB) crossing represents the major challenge for drug delivery to the central nervous system, limiting the diffusion of the therapeutic cargo. A new class of nanoscaled porous metal-organic frameworks (nanoMOFs) presents several advantages including chemical and structural versatility, exceptional drug loading capacity together with controlled release under physiological conditions, scalable synthesis and lack of toxicity. The aim of the EU-funded NeuroMOF project is to develop a bio-safe and efficient nanoMOF platform for brain delivery. Original strategies will be employed to overcome the BBB including targeting by functionalisation of the external surface of nanoMOFs with BBB-specific ligands and enzyme immobilisation – nanoMOF motion – overcoming the challenge of controlling the orientation, stability, density and distribution of the surface agent.
Objective
Neurodegenerative diseases severely affect patients’ health resulting in poor quality life and significant impact on global healthcare costs. The mayor challenge is the bypass of the blood-brain barrier (BBB), limiting the diffusion of therapeutic cargo to the central nervous system (CNS). Although emerging technologies based on nanomedicine (liposomes, polymers, etc.) are a promising approach to overcome the BBB, their clinical application is still limited by their lack of in vivo efficacy.
In view of this scenario, a new class of nanoscaled porous Metal-Organic Frameworks (nanoMOFs) has attracted great attention in the biomedical domain. NanoMOFs present several advantages compared to classic nanocarriers: i) their chemical & structural versatility, allowing a suitable biocompatibility and the potential control of their in vivo fate, ii) exceptional loading of challenging ingredients (cosmetics, enzymes, drugs...) together with controlled release under physiological conditions; iii) green and scalable synthesis; iv) lack of in vitro & in vivo toxicity; v) interesting imaging properties. Latest biomedical advances have been focussed to tackle typical administration routes (e.g. oral, intravenous or cutaneous). However, the targeted delivery to the brain has not been under the spotlight within the scientific community.
Thus, the aim of this proposal is to develop a biosafe and efficient nanoMOF platform for brain delivery. Two original strategies will be undertaken to overcome the BBB: targeting by external functionalization with BBB-specific ligands & enzyme immobilization (self-propelled nanomotors), facing up the challenge to control the orientation, stability, density and distribution (symmetric/asymmetric) of the surface agent. Apart from a full physicochemical characterization of these prototypes, BBB crossing will be first assessed by simple and 3D in vitro models and finally, by preliminary in vivo assays.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
28935 Mostoles Madrid
Spain