NeuroMOF · Self-propelled Metal-Organic Framework nanocarriers as promising brain delivery platform
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-07-01 → 2023-06-30
- EU contribution
- €160,932
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Self-propelled Metal-Organic Framework nanocarriers as promising brain delivery platform
This MSCA-IF project has addressed a challenging objective: the presence of the blood-brain barrier (BBB) has limited the treatments of neurological diseases since it constrains the drug delivery to the brain. Although novel nanomedicines have emerged as promising alternatives to overcome the BBB, their clinical application is still limited by their lack of in vivo efficacy. In this context, NeuroMOF has proposed the design of a biosafe and efficient tailored drug delivery system based on nanoscaled porous Metal Organic Frameworks (nanoMOFs) for brain delivery. To achieve this goal, two original targeting strategies by a suitable macromolecule immobilization: 1) MOF targeting (external functionalization with BBB-specific ligands) & 2) MOF motion (self-propelled nanomotors using enzymes, MOFtor). Apart from a complete characterization, we have been able to evaluate their BBB crossing in a 3D in vitro model along with their preliminary in vivo performance. This achieved progress has been related mainly with several of the tasked aims: 1) Preparation & characterization of engineered surface MOFs, monitoring their efficacy under working conditions; 2) in terms of the in vitro assays, a representative prototype of each conceived immobilized MOFs were tested, assessing both their biocompatibility & permeability in presence of specific endothelial cells; and finally, 3), their biosafety and biodistribution was also investigated at in vivo level by using female rats. Every engineered MOF prototype was carefully selected based on the proven biodistribution, biocompatibility and bioactivity assays. To achieve the challenging approach, a collaboration has been implemented between the IMDEA research group of Advanced Porous Materials Unit (APMU), led by P. Horcajada and recognized as expert in the nanoMOF synthesis, characterization & bioaplication together with the Molecular Bionics Labs, led by G. Battaglia (IBEC-Spain) in which specialists worked on the design & evaluation of chemotactic delivery systems to cross the CNS barriers by using adapted in vitro & in vivo BBB models. In this case, Dr. Hidalgo, as main beneficiary of this prestigious MSCA fellow, was in charge for overall scientific (material performance, in vitro & in vivo assays) & managerial aspects. These accomplished outcomes will serve as great proof of concept, providing new insights for effective targeted therapies based on nanoMOFs, not only at the neurological level but also for other unexplored scenarios such as pulmonary, vaginal or nasal pathways.
Data: CORDIS, © European Union
Project 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.
Original text from CORDIS.
Participants
- Fundacion IMDEA Energia · Mostoles MadridCoordinatorSpain
Links
Data: CORDIS, © European Union