In vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine)-based nanoparticles [Corrigendum]

Lopes, Cátia; Oliveira, Hugo Gonçalo; Estevão, Inês; Pires, Liliana R.; Pêgo, Ana Paula

doi:10.2147/ijn.s146417

Cited by 2 publications

(3 citation statements)

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“…Previous research has employed the tetanus toxin to alter PLGA-PEG-biotin nanoparticles for targeting neuroblastoma cells [ 49 ]. Moreover, TTC-targeted polyethyleneimine and chitosan nanocomplexes have successfully been shown to deliver non-viral gene therapeutics to primary dorsal root ganglion (DRG) and nerve crush injury models, respectively [ 20 , 22 ]. Nevertheless, the next generation of delivery platforms must prioritize carrying diverse payloads, enhancing systemic circulation, facilitating surface modification and synthesis, ensuring biocompatibility, as well as augmenting functional recovery.…”

Section: Discussionmentioning

confidence: 99%

“…Several neurotrophic factors (brain-derived neurotrophic growth factor (BDNF) [ 14 ], nerve growth factor (NGF) [ 15 , 16 ], and neurotrophin-3 [ 17 ]) have shown promise in pre-clinical investigations by promoting synaptic plasticity along with neurite and axonal growth [ 18 ]. Extensive research on delivering nucleic acid-based pro-drugs via non-viral vectors to modulate the local expression of neurotrophins and promote functional recovery has also been conducted [ 19 , 20 ]. However, low systemic half-life, pleiotropic effects, reduced cargo size, immunogenic incompatibility, and toxic side effects of large doses hamper further clinical success [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Engineering Neurotoxin-Functionalized Exosomes for Targeted Delivery to the Peripheral Nervous System

Krishnan,

Alimi,

Pan

et al. 2024

Pharmaceutics

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The administration of therapeutics to peripheral nerve tissue is challenging due to the complexities of peripheral neuroanatomy and the limitations imposed by the blood–nerve barrier (BNB). Therefore, there is a pressing need to enhance delivery effectiveness and implement targeted delivery methods. Recently, erythrocyte-derived exosomes (Exos) have gained widespread attention as biocompatible vehicles for therapeutics in clinical applications. However, engineering targeted Exos for the peripheral nervous system (PNS) is still challenging. This study aims to develop a targeted Exo delivery system specifically designed for presynaptic terminals of peripheral nerve tissue. The clostridium neurotoxin, tetanus toxin-C fragment (TTC), was tethered to the surface of red blood cell (RBC)-derived Exos via a facile and efficient bio-orthogonal click chemistry method without a catalyst. Additionally, Cyanine5 (Cy5), a reactive fluorescent tag, was also conjugated to track Exo movement in both in vitro and in vivo models. Subsequently, Neuro-2a, a mouse neuronal cell line, was treated with dye-labeled Exos with/without TTC in vitro, and the results indicated that TTC-Exos exhibited more efficient accumulation along the soma and axonal circumference, compared to their unmodified counterparts. Further investigation, using a mouse model, revealed that within 72 h of intramuscular administration, engineered TTC-Exos were successfully transported into the neuromuscular junction and sciatic nerve tissues. These results indicated that TTC played a crucial role in the Exo delivery system, improving the affinity to peripheral nerves. These promising results underscore the potential of using targeted Exo carriers to deliver therapeutics for treating peripheral neuropathies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Engineering Neurotoxin-Functionalized Exosomes for Targeted Delivery to the Peripheral Nervous System

Krishnan,

Alimi,

Pan

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

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“…Lopes et al constructed a nonviral neurotropic nanoparticle based on poly(ethylene imine), which demonstrates the capability to facilitate neuron-specific transfection following subcutaneous injection. 71 The targeting of nanoparticles to peripheral neurons is achieved using the neurotropic carboxylic fragment of the tetanus toxin (HC), which not only exhibits neurotropic properties but can also be retrogradely transported from neuron terminals to cell bodies. Following subcutaneous injection in the footpad of Wistar rats, the results obtained after five days reveal that 56% and 64% of L4 and L5 dorsal root ganglia neurons, respectively, exhibited expression of the reporter protein.…”

Section: Strategies For Nanoparticle-mediated Drug Deliverymentioning

confidence: 99%

Nanoparticle-Facilitated Therapy: Advancing Tools in Peripheral Nerve Regeneration

Shi,

Ou,

Cheng

2024

IJN

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Peripheral nerve injuries, arising from a diverse range of etiologies such as trauma and underlying medical conditions, pose substantial challenges in both clinical management and subsequent restoration of functional capacity. Addressing these challenges, nanoparticles have emerged as a promising therapeutic modality poised to augment the process of peripheral nerve regeneration. However, a comprehensive elucidation of the complicated mechanistic foundations responsible for the favorable effects of nanoparticle-based therapy on nerve regeneration remains imperative. This review aims to scrutinize the potential of nanoparticles as innovative therapeutic carriers for promoting peripheral nerve repair. This review encompasses an in-depth exploration of the classifications and synthesis methodologies associated with nanoparticles. Additionally, we discuss and summarize the multifaceted roles that nanoparticles play, including neuroprotection, facilitation of axonal growth, and efficient drug delivery mechanisms. Furthermore, we present essential considerations and highlight the potential synergies of integrating nanoparticles with emerging technologies. Through this comprehensive review, we highlight the indispensable role of nanoparticles in propelling advancements in peripheral nerve regeneration.

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In vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine)-based nanoparticles [Corrigendum]

Cited by 2 publications

References 0 publications

Engineering Neurotoxin-Functionalized Exosomes for Targeted Delivery to the Peripheral Nervous System

Engineering Neurotoxin-Functionalized Exosomes for Targeted Delivery to the Peripheral Nervous System

Nanoparticle-Facilitated Therapy: Advancing Tools in Peripheral Nerve Regeneration

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