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Mannose-coated nanozyme for relief from chemotherapy-induced peripheral neuropathic pain.

ABSTRACT: Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a progressive and disturbing peripheral neuropathy with currently no effective treatment. Aberrant production of reactive oxygen species (ROS) in macrophages near peripheral nerves plays a dominant role in CIPNP; however, traditional ROS scavengers have difficulty maintaining viability to target macrophages in vivo. Mannose-coated superparamagnetic iron oxide nanoparticles (mSPIONs) were synthesized to treat CIPNP. The anti-ROS and anti-inflammatory effects of mSPIONs were assessed in J774A.1 cells and sciatic nerves in a nociception mouse model induced with vincristine (VCR). We found that the mSPIONs significantly reduced ROS levels in vitro and in vivo. Furthermore, mSPIONs administration specifically reduced IL-6 and TNF-α levels in macrophages near the sciatic nerve and relieved VCR-induced peripheral neuropathic pain. Inhibition of the VCR-upregulated HIF1α/NF-κB signaling pathway may be involved in the alleviation of inflammation. These results provide a new approach for relieving CIPNP using a nanozyme.

SUBMITTER: Liu H

PROVIDER: S-EPMC10074233 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Mannose-coated nanozyme for relief from chemotherapy-induced peripheral neuropathic pain.

Liu Hu H Qing Xin X Peng Lijun L Zhang Ding D Dai Wei W Yang Zhilai Z Zhang Jiqian J Liu Xuesheng X

iScience 20230317 4

Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a progressive and disturbing peripheral neuropathy with currently no effective treatment. Aberrant production of reactive oxygen species (ROS) in macrophages near peripheral nerves plays a dominant role in CIPNP; however, traditional ROS scavengers have difficulty maintaining viability to target macrophages <i>in vivo</i>. Mannose-coated superparamagnetic iron oxide nanoparticles (mSPIONs) were synthesized to treat CIPNP. The anti-ROS a ...[more]

PMID: 37034991

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Project description:Chemotherapy-induced peripheral neuropathy is a challenging condition to treat, and arises due to severe, dose-limiting toxicity of chemotherapeutic drugs such as paclitaxel. This often results in debilitating sensory and motor deficits that are not effectively prevented or alleviated by existing therapeutic interventions. Recent studies have demonstrated the therapeutic effects of Meteorin, a neurotrophic factor, in reversing neuropathic pain in rodent models of peripheral nerve injury induced by physical trauma. Here, we sought to investigate the potential antinociceptive effects of recombinant mouse Meteorin (rmMeteorin) using a paclitaxel-induced peripheral neuropathy model in male and female mice. Paclitaxel treatment (4 × 4 mg/kg, i.p.) induced hind paw mechanical hypersensitivity by day 8 after treatment. Thereafter, in a reversal dosing paradigm, five repeated injections of rmMeteorin (.5 and 1.8 mg/kg s.c. respectively) administered over 9 days produced a significant and long-lasting attenuation of mechanical hypersensitivity in both sexes. Additionally, administration of rmMeteorin ( .5 and 1.8 mg/kg), initiated before and during paclitaxel treatment (prevention dosing paradigm), reduced the establishment of hind paw mechanical hypersensitivity. Repeated systemic administration of rmMeteorin in both dosing paradigms decreased histochemical signs of satellite glial cell reactivity as measured by glutamine synthetase and connexin 43 protein expression in the dorsal root ganglion. Additionally, in the prevention administration paradigm rmMeteorin had a protective effect against paclitaxel-induced loss of intraepidermal nerve fibers. Our findings indicate that rmMeteorin has a robust and sustained antinociceptive effect in the paclitaxel-induced peripheral neuropathy model and the development of recombinant human Meteorin could be a novel and effective therapeutic for chemotherapy-induced peripheral neuropathy treatment. PERSPECTIVE: Chemotherapy neuropathy is a major clinical problem that decreases quality of life for cancer patients and survivors. Our experiments demonstrate that Meteorin treatment alleviates pain-related behaviors, and signs of neurotoxicity in a mouse model of paclitaxel neuropathy.

Dataset Information

Mannose-coated nanozyme for relief from chemotherapy-induced peripheral neuropathic pain.

Publications

Mannose-coated nanozyme for relief from chemotherapy-induced peripheral neuropathic pain.

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