Nanomedicine for treating spinal cord injury

Tyler, Jacqueline Y.; Xu, Xiao–Ming; Cheng, Ji

doi:10.1039/c3nr00957b

Cited by 66 publications

(58 citation statements)

References 165 publications

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“…The body's pathophysiologial responses to injury eventually results in axonal disruption, glial scarring, myelin degradation, and the expression of molecules that inhibit axon growth [60]. selected an RNA aptamer that binds to the Nogo-66 receptor (NgR), a receptor involved in the regulation of axon regeneration [61].…”

Section: Aptamers For the Treatment Of Spinal Cord Injurymentioning

confidence: 99%

Aptamers as Promising Molecular Recognition Elements for Diagnostics and Therapeutics in the Central Nervous System

McConnell

Holahan

DeRosa

2014

Nucleic Acid Therapeutics

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Oligonucleotide aptamers are short, synthetic, single-stranded DNA or RNA able to recognize and bind to a multitude of targets ranging from small molecules to cells. Aptamers have emerged as valuable tools for fundamental research, clinical diagnosis, and therapy. Due to their small size, strong target affinity, lack of immunogenicity, and ease of chemical modification, aptamers are an attractive alternative to other molecular recognition elements, such as antibodies. Although it is a challenging environment, the central nervous system and related molecular targets present an exciting potential area for aptamer research. Aptamers hold promise for targeted drug delivery, diagnostics, and therapeutics. Here we review recent advances in aptamer research for neurotransmitter and neurotoxin targets, demyelinating disease and spinal cord injury, cerebrovascular disorders, pathologies related to protein aggregation (Alzheimer's, Parkinson's, and prions), brain cancer (glioblastomas and gliomas), and regulation of receptor function. Challenges and limitations posed by the blood brain barrier are described. Future perspectives for the application of aptamers to the central nervous system are also discussed.

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Section: Aptamers For the Treatment Of Spinal Cord Injurymentioning

confidence: 99%

Aptamers as Promising Molecular Recognition Elements for Diagnostics and Therapeutics in the Central Nervous System

McConnell

Holahan

DeRosa

2014

Nucleic Acid Therapeutics

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“…Given the poor prognosis associated with spinal cord injury or nerve damage (3,4), there is a strong need to develop more effective therapeutics (5). Forces are among the most effective known stimuli for promoting axonal elongation.…”

Section: Introductionmentioning

confidence: 99%

Measurement of Subcellular Force Generation in Neurons

O'Toole

Lamoureux

Miller

2015

Biophysical Journal

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Forces are important for neuronal outgrowth during the initial wiring of the nervous system and after trauma, yet subcellular force generation over the microtubule-rich region at the rear of the growth cone and along the axon has never, to our knowledge, been directly measured. Because previous studies have indicated microtubule polymerization and the microtubule-associated proteins Kinesin-1 and dynein all generate forces that push microtubules forward, a major question is whether the net forces in these regions are contractile or expansive. A challenge in addressing this is that measuring local subcellular force generation is difficult. Here we develop an analytical mathematical model that describes the relationship between unequal subcellular forces arranged in series within the neuron and the net overall tension measured externally. Using force-calibrated towing needles to measure and apply forces, in combination with docked mitochondria to monitor subcellular strain, we then directly measure force generation over the rear of the growth cone and along the axon of chick sensory neurons. We find the rear of the growth cone generates 2.0 nN of contractile force, the axon generates 0.6 nN of contractile force, and that the net overall tension generated by the neuron is 1.3 nN. This work suggests that the forward bulk flow of the cytoskeletal framework that occurs during axonal elongation and growth-cone pauses arises because strong contractile forces in the rear of the growth cone pull material forward.

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“…As a result, these fascinating supramolecular assemblies can become viable delivery vehicles for a diversity of biomedical applications. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] In this context, the development of strategies to monitor their translocation across soft matrices in real time, without significant perturbations of the sample, would be particularly valuable. If available, such methods would offer the opportunity to investigate and optimize the transport properties of the nanocarriers as well as facilitate the rationalization of the mechanisms responsible for their cellular internalization.…”

Section: Introductionmentioning

confidence: 99%

Photoactivatable BODIPYs Designed To Monitor the Dynamics of Supramolecular Nanocarriers

Zhang¹,

Swaminathan²,

Tang³

et al. 2015

J. Am. Chem. Soc.

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Self-assembling nanoparticles of amphiphilic polymers can transport hydrophobic molecules across hydrophilic media and, as a result, can be valuable delivery vehicles for a diversity of biomedical applications. Strategies to monitor their dynamics noninvasively and in real time are, therefore, essential to investigate their translocation within soft matrices and, possibly, rationalize the mechanisms responsible for their diffusion in biological media. In this context, we designed molecular guests with photoactivatable fluorescence for these supramolecular hosts and demonstrated that the activation of the fluorescent cargo, under optical control, permits the tracking of the nanocarrier translocation across hydrogel matrices with the sequential acquisition of fluorescence images. In addition, the mild illumination conditions sufficient to implement these operating principles permit fluorescence activation within developing Drosophila melanogaster embryos and enable the monitoring of the loaded nanocarriers for long periods of time with no cytotoxic effects and no noticeable influence on embryogenesis. These photoresponsive compounds combine a borondipyrromethene (BODIPY) chromophore and a photocleavable oxazine within their covalent skeleton. Under illumination at an appropriate activation wavelength, the oxazine ring cleaves irreversibly to bring the adjacent BODIPY fragment in conjugation with an indole heterocycle. This structural transformation shifts bathochromically the BODIPY absorption and permits the selective excitation of the photochemical product with concomitant fluorescence. In fact, these operating principles allow the photoactivation of BODIPY fluorescence with large brightness and infinite contrast. Thus, our innovative structural design translates into activatable fluorophores with excellent photochemical and photophysical properties as well as provides access to a general mechanism for the real-time tracking of supramolecular nanocarriers in hydrophilic matrices.

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Nanomedicine for treating spinal cord injury

Cited by 66 publications

References 165 publications

Aptamers as Promising Molecular Recognition Elements for Diagnostics and Therapeutics in the Central Nervous System

Aptamers as Promising Molecular Recognition Elements for Diagnostics and Therapeutics in the Central Nervous System

Measurement of Subcellular Force Generation in Neurons

Photoactivatable BODIPYs Designed To Monitor the Dynamics of Supramolecular Nanocarriers

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