Rapid fluorescence imaging of spinal cord following epidural administration of a nerve-highlighting fluorophore

Liu, Wanguo; Gu, Rui; Zhu, Qingsan; Xiao, Chunsheng; Huang, Lanfeng; Zhuang, Xiaoxi; Zhang, Jingzhe; Liu, Lidi; Ma, Ben; Yang, Huailin; Ma, Jun; Hu, Zhang; Tang, Cheng‐Lin; Chen, Xuesi

doi:10.7150/thno.18962

Cited by 16 publications

(9 citation statements)

References 57 publications

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“…Myelin is known to be present in low abundance or be absent in autonomic nerves, which could limit the use of free dyes to highlight these fine but crucial nerves 29 , 30 . Topical and epidural application of free dyes has been used to locally label nerves in animal models; however, these approaches may be limited in flexibility during human surgeries as tissue is removed and the field of view changes 20 , 31 . Anti-ganglioside antibodies have specific targeting but have long blood half-lives, which would likely require injection multiple days before surgery and may be more likely to elicit an immune response 32 , 33 .…”

Section: Discussionmentioning

confidence: 99%

Nerve-targeted probes for fluorescence-guided intraoperative imaging

et al. 2018

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A fundamental goal of many surgeries is nerve preservation, as inadvertent injury can lead to patient morbidity including numbness, pain, localized paralysis and incontinence. Nerve identification during surgery relies on multiple parameters including anatomy, texture, color and relationship to surrounding structures using white light illumination. We propose that fluorescent labeling of nerves can enhance the contrast between nerves and adjacent tissue during surgery which may lead to improved outcomes.Methods: Nerve binding peptide sequences including HNP401 were identified by phage display using selective binding to dissected nerve tissue. Peptide dye conjugates including FAM-HNP401 and structural variants were synthesized and screened for nerve binding after topical application on fresh rodent and human tissue and in-vivo after systemic IV administration into both mice and rats. Nerve to muscle contrast was quantified by measuring fluorescent intensity after topical or systemic administration of peptide dye conjugate.Results: Peptide dye conjugate FAM-HNP401 showed selective binding to human sural nerve with 10.9x fluorescence signal intensity (1374.44 ± 425.96) compared to a previously identified peptide FAM-NP41 (126.17 ± 61.03). FAM-HNP401 showed nerve-to-muscle contrast of 3.03 ± 0.57. FAM-HNP401 binds and highlight multiple human peripheral nerves including lower leg sural, upper arm medial antebrachial as well as autonomic nerves isolated from human prostate.Conclusion: Phage display has identified a novel peptide that selectively binds to ex-vivo human nerves and in-vivo using rodent models. FAM-HNP401 or an optimized variant could be translated for use in a clinical setting for intraoperative identification of human nerves to improve visualization and potentially decrease the incidence of intra-surgical nerve injury.

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Section: Discussionmentioning

confidence: 99%

Nerve-targeted probes for fluorescence-guided intraoperative imaging

et al. 2018

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“…Criteria for successful model preparation were as follows: the impact site exhibited hemorrhage and edema, hind limbs exhibited retractable flapping, tail exhibited spasmodic wagging, and animal developed sluggish paralysis. 27 , 28 After surgery, the muscle, fascia, and skin were closed in layers, and the external skin was disinfected with iodophor. The animals were resuscitated in an incubator and provided with adequate food and water.…”

Section: Methodsmentioning

confidence: 99%

Minocycline-Loaded Poly(α-Lipoic Acid)–Methylprednisolone Prodrug Nanoparticles for the Combined Anti-Inflammatory Treatment of Spinal Cord Injury

Liu¹,

Luo²,

Liu³

et al. 2022

IJN

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Purpose Traumatic spinal cord injury (TSCI) induces a powerful inflammatory response that can significantly exacerbate the extent and severity of neural damage (termed as “secondary injury”). Thus, the suppression of inflammation is crucial for reducing neurological dysfunction following TSCI. However, the conventional anti-inflammatory drugs show limited efficacy because of poor penetration and release kinetics at the injury site. This study describes the design, synthesis, release kinetics, biosafety, and preclinical efficacy of minocycline (MC)-loaded poly(α-lipoic acid)–methylprednisolone (PαLA-MP) prodrug nanoparticles (NPs) for the combined anti-inflammatory treatment of TSCI. Methods NPs were produced by conjugating MP to PαLA and then loading MC. The NP structure was confirmed through 1 H nuclear magnetic resonance ( 1 H NMR), Fourier transform infrared spectroscopy, ultraviolet–visible absorption spectroscopy, gel permeation chromatography, dynamic light scattering, and transmission electron microscopy. Drug-loading content and efficacy were measured using high-performance liquid chromatography (HPLC) or 1 H NMR and release kinetics through HPLC. Biosafety was examined using the MTT assay, cell penetration efficiency using confocal microscopy, and flow cytometry using Cyanine5 (Cy5)-labeled MC-PαLA-MP NPs, effects on injury-induced pro-inflammatory cytokine release using enzyme-linked immunosorbent assays and immunofluorescence, and treatment efficacy by measuring motor recovery in a rat model of TSCI. Results The MC-PαLA-MP NPs exhibited high biocompatibility and released 81% MC and 54% MP within 24 h under TSCI-like conditions, effectively reducing 40% of pro-inflammatory cytokine release both in cultures and injured rat spinal cord tissues. Systemic injection increased the Basso, Beattie, Bresnahan score of TSCI rats from 2.33 ± 0.52 to 8.83 ± 1.83 in 8 weeks, providing effective neuroprotection and enhanced exercise recovery in the TSCI rats. Conclusion The MC-PαLA-MP NPs can mitigate secondary inflammation and preserve motor function following experimental TSCI, which suggests their potential for clinical application.

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“…[9][10][11] This section introduces the mechanisms and methods through which NP systems reach surgical target regions, thereby helping operations achieve the abovementioned requirements. and the prevention of damage to nearby structures, such as important vessels, nerves, and organs.…”

Section: Nanotechnology For Enhanced Accumulation Of Nms In Surgical mentioning

confidence: 99%

Advanced Nanotechnology Leading the Way to Multimodal Imaging‐Guided Precision Surgical Therapy

et al. 2019

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Surgical resection is the primary and most effective treatment for most patients with solid tumors. However, patients suffer from postoperative recurrence and metastasis. In the past years, emerging nanotechnology has led the way to minimally invasive, precision and intelligent oncological surgery after the rapid development of minimally invasive surgical technology. Advanced nanotechnology in the construction of nanomaterials (NMs) for precision imaging-guided surgery (IGS) as well as surgery-assisted synergistic therapy is summarized, thereby unlocking the advantages of nanotechnology in multimodal IGS-assisted precision synergistic cancer therapy. First, mechanisms and principles of NMs to surgical targets are briefly introduced. Multimodal imaging based on molecular imaging technologies provides a practical method to achieve intraoperative visualization with high resolution and deep tissue penetration. Moreover, multifunctional NMs synergize surgery with adjuvant therapy (e.g., chemotherapy, immunotherapy, phototherapy) to eliminate residual lesions. Finally, key issues in the development of ideal theranostic NMs associated with surgical applications and challenges of clinical transformation are discussed to push forward further development of NMs for multimodal IGS-assisted precision synergistic cancer therapy.

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Rapid fluorescence imaging of spinal cord following epidural administration of a nerve-highlighting fluorophore

Cited by 16 publications

References 57 publications

Nerve-targeted probes for fluorescence-guided intraoperative imaging

Nerve-targeted probes for fluorescence-guided intraoperative imaging

Minocycline-Loaded Poly(α-Lipoic Acid)–Methylprednisolone Prodrug Nanoparticles for the Combined Anti-Inflammatory Treatment of Spinal Cord Injury

Advanced Nanotechnology Leading the Way to Multimodal Imaging‐Guided Precision Surgical Therapy

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