摘要
Acute inflammation is a central component in the progression of spinal cord injury(SCI).Anti-inflammatory drugs used in the clinic are often administered systemically at high doses,which can paradoxically increase inflammation and result in drug toxicity.A cluster-like mesoporous silica/arctigenin/CAQK composite(MSN-FC@ARCG)drug delivery system was designed to avoid systemic side effects of high-dose therapy by enabling site-specific drug delivery to the spinal cord.In this nanosystem,mesoporous silica was modified with the FITC fluorescent molecule and CAQK peptides that target brain injury and SCI sites.The size of the nanocarrier was kept at approximately 100 nm to enable penetration of the blood–brain barrier.Arctigenin,a Chinese herbal medicine,was loaded into the nanosystem to reduce inflammation.The in vivo results showed that MSN-FC@ARC-G could attenuate inflammation at the injury site.Behavior and morphology experiments suggested that MSN-FC@ARC-G could diminish local microenvironment damage,especially reducing the expression of interleukin-17(IL-17) and IL-17-related inflammatory factors,inhibiting the activation of astrocytes,thus protecting neurons and accelerating the recovery of SCI.Our study demonstrated that this novel,silica-based drug delivery system has promising potential for clinical application in SCI therapy.
Acute inflammation is a central component in the progression of spinal cord injury(SCI).Anti-inflammatory drugs used in the clinic are often administered systemically at high doses,which can paradoxically increase inflammation and result in drug toxicity.A cluster-like mesoporous silica/arctigenin/CAQK composite(MSN-FC@ARCG)drug delivery system was designed to avoid systemic side effects of high-dose therapy by enabling site-specific drug delivery to the spinal cord.In this nanosystem,mesoporous silica was modified with the FITC fluorescent molecule and CAQK peptides that target brain injury and SCI sites.The size of the nanocarrier was kept at approximately 100 nm to enable penetration of the blood–brain barrier.Arctigenin,a Chinese herbal medicine,was loaded into the nanosystem to reduce inflammation.The in vivo results showed that MSN-FC@ARC-G could attenuate inflammation at the injury site.Behavior and morphology experiments suggested that MSN-FC@ARC-G could diminish local microenvironment damage,especially reducing the expression of interleukin-17(IL-17) and IL-17-related inflammatory factors,inhibiting the activation of astrocytes,thus protecting neurons and accelerating the recovery of SCI.Our study demonstrated that this novel,silica-based drug delivery system has promising potential for clinical application in SCI therapy.
基金
supported by the National Natural Science Foundation of China(Nos.31670969,51302089,and 31571030)
the Fundamental Research Funds for the Central Universities(No.21617428)
Key Program of Traditional Chinese Medicine of Guangdong Province(No.20173018)
The Science and Technology Program of Jiangmen City of China(No.2017A2004)
Natural Science Foundation of Guangdong Province(No.2018A030313576)
Science and Technology Program of Guangzhou(No.201803010001)
