Translational challenges in advancing regenerative therapy for treating neurological disorders using nanotechnology

Nemeth, Christina L.; Fine, Amena Smith; Fatemi, Ali

doi:10.1016/j.addr.2019.05.003

Cited by 26 publications

(9 citation statements)

References 72 publications

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“…In most known neurodegenerative diseases, neural cell structures are affected and eventually lose function. Therefore, successful regenerative therapy can be achieved by replacement of damaged neurons with the new ones or by restoration of neural tissue/organs [2]. The progress of cell therapy techniques in transplantation of stem cells has improved the shortage of neuron function in both acute and chronic neurodegenerative disorders.…”

Section: Cell Therapy Of Neural System Using Stem Cellsmentioning

confidence: 99%

“…There are no treatments for neurodegenerative diseases and the currently used medicines can only reduce the symptoms or slow down the progress of disease [1]. Successful design of therapies for a patient population needs careful consideration involving collaboration between clinicians, neuroscientists and bioengineers to cover both the disease aspects and clinical requirements [2].…”

Section: Introductionmentioning

confidence: 99%

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Application of Nanotechnology in Stem-Cell-Based Therapy of Neurodegenerative Diseases

et al. 2020

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In addition to adverse health outcomes, neurological disorders have serious societal and economic impacts on patients, their family and society as a whole. There is no definite treatment for these disorders, and current available drugs only slow down the progression of the disease. In recent years, application of stem cells has been widely advanced due to their potential of self-renewal and differentiation to different cell types which make them suitable candidates for cell therapy. In particular, this approach offers great opportunities for the treatment of neurodegenerative disorders. However, some major issues related to stem-cell therapy, including their tumorigenicity, viability, safety, metastases, uncontrolled differentiation and possible immune response have limited their application in clinical scales. To address these challenges, a combination of stem-cell therapy with nanotechnology can be a solution. Nanotechnology has the potential of improvement of stem-cell therapy by providing ideal substrates for large scale proliferation of stem cells. Application of nanomaterial in stem-cell culture will be also beneficial to modulation of stem-cell differentiation using nanomedicines. Nanodelivery of functional compounds can enhance the efficiency of neuron therapy by stem cells and development of nanobased techniques for real-time, accurate and long-lasting imaging of stem-cell cycle processes. However, these novel techniques need to be investigated to optimize their efficiency in treatment of neurologic diseases.

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Section: Cell Therapy Of Neural System Using Stem Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Application of Nanotechnology in Stem-Cell-Based Therapy of Neurodegenerative Diseases

et al. 2020

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“…These inhibitors enable the inhibition of the fibrillation process of Aβ or hIAPP, or even both. However, due to the limitations of low selectivity, poor stability, poor biocompatibility, and low permeability across the blood–brain barrier, , most of them have not been successfully applied in clinical treatment, especially for the co-fibrillation between different amyloid peptides.…”

Section: Introductionmentioning

confidence: 99%

Electric Field Effect on Inhibiting the Co-fibrillation of Amyloid Peptides by Modulating the Aggregation Pathway

Zhang

et al. 2022

Langmuir

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With the revelation of the close link between Alzheimer's disease (AD) and type II diabetes (T2D) and the possible assembly of multiple amyloid peptides therein, it is critical to understand and regulate the co-fibrillation pathway between related amyloid peptides. Here, we show experimentally and theoretically that electric field (EF) inhibited hybrid amyloid fibrillation of β-amyloid peptide (Aβ) and human islet amyloid peptide (hIAPP) by modulating the hetero-aggregation pathway. Experimental results confirm that the β-sheet secondary structure of amyloid peptides would be disrupted under small static EF and accompanied by transforming fibril aggregates into amorphous particles in vitro. Molecular dynamics simulations further demonstrate that even with the transformation of the secondary structure from β-sheet to random coil, the strong interaction between Aβ and hIAPP peptides would remain largely unaffected under the small static EF, leading to the formation of amorphous nanoparticles observed in the experiments. This inhibitory effect of EF on the co-fibrillation of multiple amyloid peptides might contribute to reducing the mutual deterioration of different degenerative diseases and show great potential for the noninvasive treatment of amyloid-related diseases.

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“…Recent advances in nanotechnology have revealed various biocompatible nanomaterials that exhibit exceptional potential in molecular imaging, [29] multiplexed profiling of disease biomarkers, [30] and targeted therapy. [31] Carbon dots as quasi-zero dimensional carbon-based luminescent nanomaterials have recently attracted widespread attention, which is largely due to their versatile physical properties, such as high photostability, [32,33] good biocompatibility, [34] surface modifiability, [35] and excellent water solubility. Previous reports have revealed that carbon dots could be used for bone-related disease treatment.…”

Section: Introductionmentioning

confidence: 99%

Multifunctional Alendronate‐PEI Carbon Dots for the Treatment of Bone‐Destructive Diseases via Bidirectional Regulation of Osteoblast‐Osteoclast Function

Zhang

Wang

et al. 2022

Advanced Therapeutics

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Bone damage results from the imbalance of bone homeostasis maintained by osteoblast-regulated bone formation and osteoclast-mediated bone resorption. Conventional drug therapy and gene therapy may not optimally regulate the bone remodeling process due to the unitary pharmacological mechanism of drug and the safety and targeting of gene vectors. In the present study, multifunctional fluorescent alendronate-polyethyleneimine carbon dots (Alen-PEI CDs) are innovatively synthesized, which have excellent biocompatibility, selective bone targeting, gene carrying capacity, and anti-bone absorption effect. As gene vectors, bone morphogenic protein 2 (BMP2) gene-loaded Alen-PEI CDs greatly enhance osteoblast differentiation and bone regeneration. Notably, Alen-PEI CDs are found to directly inhibit the formation and function of osteoclasts, effectively attenuating the LPS-induced skull osteolysis in mice. Furthermore, their cumulative toxicity is lower than that of Alen, indicating their potential as an anti-bone resorptive nanodrug. These results show that the bone-targeting Alen-PEI CDs significantly reverse the imbalance of bone homeostasis through a dual-directional mechanism-directly suppressing bone resorption and indirectly inducing bone formation by transfection of osteogenic therapeutic genes. Overall, the study expands the application for carbon dots in biomedicine, providing new insights for the further development of novel selectively targeted multifunctional nanodrugs for the treatment of bone-destructive diseases.

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Translational challenges in advancing regenerative therapy for treating neurological disorders using nanotechnology

Cited by 26 publications

References 72 publications

Application of Nanotechnology in Stem-Cell-Based Therapy of Neurodegenerative Diseases

Application of Nanotechnology in Stem-Cell-Based Therapy of Neurodegenerative Diseases

Electric Field Effect on Inhibiting the Co-fibrillation of Amyloid Peptides by Modulating the Aggregation Pathway

Multifunctional Alendronate‐PEI Carbon Dots for the Treatment of Bone‐Destructive Diseases via Bidirectional Regulation of Osteoblast‐Osteoclast Function

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