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      KCI등재 SCIE SCOPUS

      pH/Temperature Responsive Curcumin-Loaded Micelle Nanoparticles Promote Functional Repair after Spinal Cord Injury in Rats via Modulation of Inflammation

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      https://www.riss.kr/link?id=A108769946

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      다국어 초록 (Multilingual Abstract)

      BACKGROUND: The formation of an inhibitory inflammatory microenvironment after spinal cord injury (SCI) remains a great challenge for nerve regeneration. The poor local microenvironment exacerbates nerve cell death; therefore, the reconstruction of a favorable microenvironment through small-molecule drugs is a promising strategy for promoting nerve regeneration.
      METHODS: In the present study, we synthesized curcumin-loaded micelle nanoparticles (Cur-NPs) to increase curcumin bioavailability and analyzed the physical and chemical properties of Cur-NPs by characterization experiments. We established an in vivo SCI model in rats and examined the ability of hind limb motor recovery using Basso–Beattie– Bresnahan scoring and hind limb trajectory assays. We also analyzed neural regeneration after SCI using immunofluorescence staining.
      RESULTS: The nanoparticles achieved the intelligent responsive release of curcumin while improving curcumin bioavailability. Most importantly, the released curcumin attenuated local inflammation by modulating the polarization of macrophages from an M1 pro-inflammatory phenotype to an M2 anti-inflammatory phenotype. M2-type macrophages can promote cell differentiation, proliferation, matrix secretion, and reorganization by secreting or expressing pro-repair cytokines to reduce the inflammatory response. The enhanced inflammatory microenvironment supported neuronal regeneration, nerve remyelination, and reduced scar formation. These effects facilitated functional repair in rats, mainly in the form of improved hindlimb movements.
      CONCLUSION: Here, we synthesized pH/temperature dual-sensitive Cur-NPs. While improving the bioavailability of the drug, they were also able to achieve a smart responsive release in the inflammatory microenvironment that develops after SCI. The Cur-NPs promoted the regeneration and functional recovery of nerves after SCI through anti-inflammatory effects, providing a promising strategy for the repair of SCIs.
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      BACKGROUND: The formation of an inhibitory inflammatory microenvironment after spinal cord injury (SCI) remains a great challenge for nerve regeneration. The poor local microenvironment exacerbates nerve cell death; therefore, the reconstruction of a ...

      BACKGROUND: The formation of an inhibitory inflammatory microenvironment after spinal cord injury (SCI) remains a great challenge for nerve regeneration. The poor local microenvironment exacerbates nerve cell death; therefore, the reconstruction of a favorable microenvironment through small-molecule drugs is a promising strategy for promoting nerve regeneration.
      METHODS: In the present study, we synthesized curcumin-loaded micelle nanoparticles (Cur-NPs) to increase curcumin bioavailability and analyzed the physical and chemical properties of Cur-NPs by characterization experiments. We established an in vivo SCI model in rats and examined the ability of hind limb motor recovery using Basso–Beattie– Bresnahan scoring and hind limb trajectory assays. We also analyzed neural regeneration after SCI using immunofluorescence staining.
      RESULTS: The nanoparticles achieved the intelligent responsive release of curcumin while improving curcumin bioavailability. Most importantly, the released curcumin attenuated local inflammation by modulating the polarization of macrophages from an M1 pro-inflammatory phenotype to an M2 anti-inflammatory phenotype. M2-type macrophages can promote cell differentiation, proliferation, matrix secretion, and reorganization by secreting or expressing pro-repair cytokines to reduce the inflammatory response. The enhanced inflammatory microenvironment supported neuronal regeneration, nerve remyelination, and reduced scar formation. These effects facilitated functional repair in rats, mainly in the form of improved hindlimb movements.
      CONCLUSION: Here, we synthesized pH/temperature dual-sensitive Cur-NPs. While improving the bioavailability of the drug, they were also able to achieve a smart responsive release in the inflammatory microenvironment that develops after SCI. The Cur-NPs promoted the regeneration and functional recovery of nerves after SCI through anti-inflammatory effects, providing a promising strategy for the repair of SCIs.

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      참고문헌 (Reference)

      1 Kim Do-Hun ; Cho Hyun-Ju ; Park Chul-Yong ; 조명수 ; Kim Dong-Wook, "Transplantation of PSA-NCAM-Positive Neural Precursors from Human Embryonic Stem Cells Promotes Functional Recovery in an Animal Model of Spinal Cord Injury" 한국조직공학과 재생의학회 19 (19): 1349-1358, 2022

      2 Salewski RP, "Transplantation of Induced pluripotent stem cellderived neural stem cells mediate functional recovery following thoracic spinal cord injury through remyelination of axons" 4 : 743-754, 2015

      3 Sanivarapu R, "The potential of curcumin in treatment of spinal cord injury" 2016 : 9468193-, 2016

      4 Norenberg MD, "The pathology of human spinal cord injury : defining the problems" 21 : 429-440, 2004

      5 Milich LM, "The origin, fate, and contribution of macrophages to spinal cord injury pathology" 137 : 785-797, 2019

      6 Dunster JL, "The macrophage and its role in inflammation and tissue repair : mathematical and systems biology approaches" 8 : 87-99, 2016

      7 Li W, "The fine-tuning of thermosensitive and degradable polymer micelles for enhancing intracellular uptake and drug release in tumors" 32 : 3832-3844, 2011

      8 Bloom O, "Systemic inflammation in traumatic spinal cord injury" 325 : 113143-, 2020

      9 Liu X, "Selenium nanoparticles derived from Proteus mirabilis YC801 alleviate oxidative stress and inflammatory response to promote nerve repair in rats with spinal cord injury" 9 : rbac042-, 2022

      10 Stenudd M, "Role of endogenous neural stem cells in spinal cord injury and repair" 72 : 235-237, 2015

      1 Kim Do-Hun ; Cho Hyun-Ju ; Park Chul-Yong ; 조명수 ; Kim Dong-Wook, "Transplantation of PSA-NCAM-Positive Neural Precursors from Human Embryonic Stem Cells Promotes Functional Recovery in an Animal Model of Spinal Cord Injury" 한국조직공학과 재생의학회 19 (19): 1349-1358, 2022

      2 Salewski RP, "Transplantation of Induced pluripotent stem cellderived neural stem cells mediate functional recovery following thoracic spinal cord injury through remyelination of axons" 4 : 743-754, 2015

      3 Sanivarapu R, "The potential of curcumin in treatment of spinal cord injury" 2016 : 9468193-, 2016

      4 Norenberg MD, "The pathology of human spinal cord injury : defining the problems" 21 : 429-440, 2004

      5 Milich LM, "The origin, fate, and contribution of macrophages to spinal cord injury pathology" 137 : 785-797, 2019

      6 Dunster JL, "The macrophage and its role in inflammation and tissue repair : mathematical and systems biology approaches" 8 : 87-99, 2016

      7 Li W, "The fine-tuning of thermosensitive and degradable polymer micelles for enhancing intracellular uptake and drug release in tumors" 32 : 3832-3844, 2011

      8 Bloom O, "Systemic inflammation in traumatic spinal cord injury" 325 : 113143-, 2020

      9 Liu X, "Selenium nanoparticles derived from Proteus mirabilis YC801 alleviate oxidative stress and inflammatory response to promote nerve repair in rats with spinal cord injury" 9 : rbac042-, 2022

      10 Stenudd M, "Role of endogenous neural stem cells in spinal cord injury and repair" 72 : 235-237, 2015

      11 Beck KD, "Quantitative analysis of cellular inflammation after traumatic spinal cord injury : evidence for a multiphasic inflammatory response in the acute to chronic environment" 133 : 433-447, 2010

      12 Yardim A, "Protective effects of curcumin against paclitaxelinduced spinal cord and sciatic nerve injuries in rats" 46 : 379-395, 2021

      13 Zhou P, "Promoting 3D neuronal differentiation in hydrogel for spinal cord regeneration" 194 : 111214-, 2020

      14 Li X, "Premna microphylla Turcz leaf pectin exhibited antioxidant and anti-inflammatory activities in LPS-stimulated RAW 2647 macrophages" 349 : 129164-, 2021

      15 Nakayama M, "Polymer terminal group effects on properties of thermoresponsive polymeric micelles with controlled outer-shell chain lengths" 6 : 2320-2327, 2005

      16 Duan FX, "Neuroprotective effects of P7C3 against spinal cord injury in rats" 244 : 1680-1687, 2019

      17 Huang L, "Neuroprotective effect of curcumin against cerebral ischemia-reperfusion via mediating autophagy and inflammation" 64 : 129-139, 2018

      18 Zhang L, "NSCs migration promoted and drug delivered exosomes-collagen scaffold via a bio-specific peptide for one-step spinal cord injury repair" 10 : e2001896-, 2021

      19 Yuan Y, "Mitochondrial ROS-induced lysosomal dysfunction impairs autophagic flux and contributes to M1 macrophage polarization in a diabetic condition" 133 : 1759-1777, 2019

      20 Harigae T, "Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration" 11 : 3009-3022, 2016

      21 Chawla A, "Macrophage-mediated inflammation in metabolic disease" 11 : 738-749, 2011

      22 Akilbekova D, "Macrophage reprogramming : influence of latex beads with various functional groups on macrophage phenotype and phagocytic uptake in vitro" 103 : 262-268, 2015

      23 Kong X, "Macrophage polarization : a key event in the secondary phase of acute spinal cord injury" 21 : 941-954, 2017

      24 Kotter MR, "Macrophage depletion impairs oligodendrocyte remyelination following lysolecithin-induced demyelination" 35 : 204-212, 2001

      25 Jung KK, "Inhibitory effect of curcumin on nitric oxide production from lipopolysaccharide-activated primary microglia" 79 : 2022-2031, 2006

      26 Jiang W, "Inhibition of NLRP3 inflammasome attenuates spinal cord injury-induced lung injury in mice" 234 : 6012-6022, 2019

      27 Liu X, "Inflammatory response to spinal cord injury and its treatment" 155 : 19-31, 2021

      28 He L, "Highly bioactive zeolitic imidazolate framework-8-capped nanotherapeutics for efficient reversal of reperfusion-induced injury in ischemic stroke" 6 : eaay9751-, 2020

      29 Gaudet AD, "Glial cells shape pathology and repair after spinal cord injury" 15 : 554-577, 2018

      30 Deng W, "EMSCs build an all-in-one niche via cell-cell lipid raft assembly for promoted neuronal but suppressed astroglial differentiation of neural stem cells" 31 : e1806861-, 2019

      31 Sofroniew MV, "Dissecting spinal cord regeneration" 557 : 343-350, 2018

      32 Choi JS, "Development of surface curcumin nanoparticles modified with biological macromolecules for anti-tumor effects" 92 : 850-859, 2016

      33 Chen Y, "Curcumin promotes the proliferation, invasion of neural stem cells and formation of neurospheres via activating SDF-1/CXCR4 axis" 59 : 152-160, 2021

      34 Li W, "Curcumin promotes functional recovery and inhibits neuronal apoptosis after spinal cord injury through the modulation of autophagy" 44 : 37-45, 2021

      35 Wang F, "Curcumin attenuates intracerebral hemorrhage-induced neuronal apoptosis and neuroinflammation by suppressing JAK1/STAT1pathway" 100 : 236-245, 2022

      36 Benzer F, "Curcumin ameliorates doxorubicin-induced cardiotoxicity by abrogation of inflammation, apoptosis, oxidative DNA damage, and protein oxidation in rats" 32 : e22030-, 2018

      37 Sharma N, "Curcumin affords neuroprotection and inhibits alpha-synuclein aggregation in lipopolysaccharide-induced Parkinson’s disease model" 26 : 349-360, 2018

      38 Cowan H, "Autonomic dysreflexia in spinal cord injury" 371 : m3596-, 2020

      39 Jin W, "Anti-inflammatory effects of curcumin in experimental spinal cord injury in rats" 63 : 381-387, 2014

      40 Luo J, "An injectable and selfhealing hydrogel with controlled release of curcumin to repair spinal cord injury" 6 : 4816-4829, 2021

      41 Gao X, "An antiinflammatory and neuroprotective biomimetic nanoplatform for repairing spinal cord injury" 18 : 569-582, 2022

      42 Huang Y, "Amlodipine improves spinal cord injury repair by inhibiting motoneuronal apoptosis through autophagy upregulation" 47 : E570-E578, 2022

      43 Chen Z, "Adhesive, stretchable, and spatiotemporal delivery fibrous hydrogels harness endogenous neural stem/progenitor cells for spinal cord injury repair" 16 : 1986-1998, 2022

      44 Sravani AB, "A sensitive spectrofluorimetric method for curcumin analysis" 32 : 1517-1527, 2022

      45 Basso DM, "A sensitive and reliable locomotor rating scale for open field testing in rats" 12 : 1-21, 1995

      46 Li Z, "A reactive oxygen species-responsive hydrogel encapsulated with bone marrow derived stem cells promotes repair and regeneration of spinal cord injury" 19 : 550-568, 2022

      47 Li X, "A collagen microchannel scaffold carrying paclitaxel-liposomes induces neuronal differentiation of neural stem cells through Wnt/betacatenin signaling for spinal cord injury repair" 183 : 114-127, 2018

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