DUAL-FUNCTIONAL FLUORINATED NANOPARTICLES FOR BRAIN TARGETING AND TRANSPORT OF DRUGS INTO THE BRAIN

Description

This invention introduces a novel class of engineered dual-functional nanoparticles. These drug delivery systems are produced with lipids or polymers and are designed to overcome the restrictive nature of the blood-brain barrier (BBB). These nanoparticles are not only able to cross the BBB but also deliver therapeutic agents directly to the brain, targeting the specific regions affected by diseases like Alzheimer's and other neurodegenerative disorders. The technology is based on nanoparticles that have been surface-modified with specific molecules, enhancing their ability to penetrate the BBB. That surface modification improves the lipophilicity and metabolic stability of the nanoparticles, enabling them to cross the BBB more efficiently than conventional lipid-based or polymeric nanoparticles. In addition to this modification, these nanoparticles are further engineered with functional ligands that specifically target and bind to receptors on the endothelial cells of the BBB. This enables precise targeting of drug delivery to the brain, ensuring that therapeutic agents are delivered to the intended site while minimizing off-target effects. This targeted approach significantly reduces the systemic exposure of drugs, minimizing side effects commonly seen with other drug delivery systems that do not specifically target the brain. Additionally, these nanoparticles by themselves proved to be efficient in preventing one of the mechanisms of Alzheimer's disease. One of the most important mechanisms of the disease is the aggregation of the amyloid-beta peptide — the peptides acquire a beta-sheet conformation and aggregate, ultimately leading to the formation of amyloid plaques, which are toxic to brain cells. These nanoparticles demonstrate a measurable delay in the aggregation of the amyloid-beta peptide. The invention provides a transformative step in nanomedicine by integrating therapeutic function with delivery efficiency, offering next-generation nanoplatforms for Alzheimer's disease therapy and other neurological disorders.

Advantages

This dual-functional nanoparticle system offers several key advantages over current Alzheimer's treatments and delivery technologies.
Enhanced BBB permeability is achieved through fluorination, which increases the nanoparticle's lipophilicity and improves its ability to cross brain endothelial barriers. When combined with transferrin (Tf) targeting ligands, the system enables receptor-mediated transcytosis, leading to significantly higher brain accumulation and site-specific delivery compared to unmodified nanoparticles.
Intrinsic anti-amyloid activity is another key feature. Functionalized with fluorinated moieties, the nanoparticles can directly interact with amyloid-beta peptides, inhibiting aggregation and potentially disaggregating existing plaques. This means the carrier itself contributes to disease modification and inhibition — not just drug delivery.
Comparative experimental studies (in vitro and in vivo) confirm that these dual-functional nanoparticles outperform standard formulations in BBB penetration, brain targeting, and reduction of amyloid-beta plaque burden. Wild-type mouse models treated with these nanoparticles showed brain penetration within 2 hours of intravenous delivery, compared to placebo or control groups using unmodified nanoparticles.
The proposed dual-functional nanoparticle systems offer multi-targeted delivery, lower systemic exposure, and dual therapeutic function, representing a significant advancement in Alzheimer's nanomedicine.

Uses and Applications

There is still no cure for Alzheimer's disease. This invention addresses a critical unmet need in the AD market: the lack of effective, brain-targeted therapies that can both cross the BBB and actively interfere with amyloid-beta aggregation.
Current drugs, including cholinesterase inhibitors and NMDA antagonists, offer only symptomatic relief, while monoclonal antibody therapies (e.g., aducanumab, lecanemab) suffer from limited BBB penetration, serious side effects such as amyloid-related imaging abnormalities (ARIA), and very high costs that are difficult for patients to sustain.
The dual-functional fluorinated nanoparticle system offers a transformative alternative, acting both as a BBB-penetrating delivery vehicle and as a therapeutic agent with intrinsic anti-amyloid activity. This combination enables more effective and safer targeting of AD pathology, potentially reducing required dosages and systemic side effects.
Market segments where this technology has utility include:

• Alzheimer's disease therapeutics, a market estimated to exceed $15 billion globally by 2030
• Nanomedicine platforms for neurodegenerative disorders, including Parkinson's disease, amyotrophic lateral sclerosis (ALS), and Huntington's disease
• Targeted drug delivery systems for CNS disorders and brain cancers.

There is strong commercial interest in next-generation Alzheimer's therapeutics and CNS-targeting technologies, particularly those that address BBB limitations. Pharmaceutical companies developing monoclonal antibodies or small-molecule CNS drugs may seek to license or partner with delivery platforms such as this invention to enhance efficacy. Additionally, the modular nature of the system allows for adaptation to other neurological indications, further expanding its commercial potential.

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Applicants

UNIVERSIDAD DE MÁLAGA, UNIVERSIDADE DO PORTO (UPORTO)

Inventors

MARIA DO CARMO DA SILVA PEREIRA , JOANA ANGÉLICA DE SOUSA LOUREIRO, MEGHNA DABUR , MARIA JOÃO ALVES RAMALHO, STÉPHANIE MACHADO ANDRADE, INES MORENO GONZALEZ, LAURA VEGAS GÓMEZ

Filing Date

23/10/2025 

Protection Level: National (Spain)

Processing Status: Spanish protection application