Nanoparticles are zero-dimensional nanomaterials and, based on their nature, they can be categorized into organic, inorganic, and composites nanoparticles. Due to their unique physical and chemical properties, nanoparticles are extensively used in a variety of fields, including medicine, pharmaceutics, and food industry. Although they have the potential to improve the diagnosis and treatment of brain diseases, it is fundamentally important to develop standardized toxicological studies, which can prevent the induction of neurotoxic effects. The focus of this review is to emphasize both the beneficial and negative effects of nanoparticles on brain health.

https://www.mdpi.com/2077-0383/7/12/490/pdf

Impact of Nanoparticles on Brain Health: An Up to Date Overview.

AGuIX® are sub-5 nm nanoparticles made of a polysiloxane matrix and gadolinium chelates This nanoparticle has been recently accepted in clinical trials in association with radiotherapy This review will summarize the principal preclinical results that have led to first in man administration No evidence of toxicity has been observed during regulatory toxicity tests on two animal species (rodents and monkeys) Biodistributions on different animal models have shown passive uptake in tumours due to enhanced permeability and retention effect combined with renal elimination of the nanoparticles after intravenous administration High radiosensitizing effect has been observed with different types of irradiations in vitro and in vivo on a large number of cancer types (brain, lung, melanoma, head and neck…) The review concludes with the second generation of AGuIX nanoparticles and the first preliminary results on human

/pdf/aguix-from-bench-to-bedside-transfer-of-an-ultrasmall-2c5kulz8p3.pdf

AGuIX® from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine.

Nanoparticle formulations in the diagnosis and therapy of Alzheimer's disease.

The major neurological disorders found in a central nervous system (CNS), such as brain tumors, Alzheimer’s diseases, Parkinson’s diseases, and Huntington’s disease, have led to devastating outcomes on the human public health. Of these disorders, early diagnostics remains poor, and no treatment has been successfully discovered; therefore, they become the most life-threatening medical burdens worldwide compared to other major diseases. The major obstacles for the drug discovery are the presence of a restrictive blood–brain barrier (BBB), limiting drug entry into brains and undesired neuroimmune activities caused by untargeted drugs, leading to irreversible neuronal damages. Recent advances in nanotechnology have contributed to the development of novel nanoplatforms and effective delivering strategies to improve the CNS disorder treatment while less disturbing brain systems. The nanoscale drug carriers, including liposomes, dendrimers, viral capsids, polymeric nanoparticles, silicon nanoparticles, and magnetic/metallic nanoparticles, enable the effective drug delivery penetrating across the BBB, the aforementioned challenges in the CNS. Moreover, drugs encapsulated by the nanocarriers can reach further deeper into targeting regions while preventing the degradation. In this review, we classify novel disease hallmarks incorporated with emerging nanoplatforms, describe promising approaches for improving drug delivery to the disordered CNS, and discuss their implications for clinical practice.

https://link.springer.com/content/pdf/10.1186/s40580-018-0168-8.pdf

Therapeutic nanoplatforms and delivery strategies for neurological disorders

Amyloid fibres attract considerable interest due to their biological role in neurodegenerative diseases and their potential as functional biomaterials. Here, we describe an intrinsic signal of amyloid fibres in the near-infrared range. When combined with their recently reported blue luminescence, it paves the way towards new blueprints for the label-free detection of amyloid deposits in in vitro and in vivo contexts. The blue luminescence allows for staining-free characterization of amyloid deposits in human samples. The near-infrared signal offers promising prospects for innovative diagnostic strategies for neurodegenerative diseases—to improve medical care and for the development of new therapies. As a proof of concept, we demonstrate direct detection of amyloid deposits within brains of living, aged mice with Alzheimer’s disease using non-invasive and contrast-agent-free imaging. Ultraviolet–visible–near-infrared optical properties of amyloids open new research avenues for amyloidosis as well as for next-generation biophotonic devices.

Ultraviolet–visible–near-infrared optical properties of amyloid fibrils shed light on amyloidogenesis

Amyloidoses are characterized by the extracellular deposition of insoluble fibrillar proteinaceous aggregates highly organized into cross-β structure and referred to as amyloid fibrils. Nowadays, the diagnosis of these diseases remains tedious and involves multiple examinations while an early and accurate protein typing is crucial for the patients’ treatment. Routinely used neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) using Pittsburgh compound B, [11C]PIB, provide structural information and allow to assess the amyloid burden, respectively, but cannot discriminate between different amyloid deposits. Therefore, the availability of efficient multimodal imaging nanoparticles targeting specific amyloid fibrils would provide a minimally-invasive imaging tool useful for amyloidoses typing and early diagnosis. In the present study, we have functionalized gadolinium-based MRI nanoparticles (AGuIX) with peptides highly specific for Aβ amyloid fibrils, LPFFD and KLVFF. The capacity of such nanoparticles grafted with peptide to discriminate among different amyloid proteins, was tested with Aβ(1–42) fibrils and with mutated-(V30M) transthyretin (TTR) fibrils.

/pdf/gd-nanoparticles-functionalization-with-specific-peptides-31low9fl29.pdf

Gd-nanoparticles functionalization with specific peptides for ß-amyloid plaques targeting

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Gd-nanoparticles functionalization with specific peptides for ß-amyloid plaques targeting