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用于治疗脊髓损伤中激活星形胶质细胞的功能化纳米凝胶。

Functionalized nanogel for treating activated astrocytes in spinal cord injury.

机构信息

Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via mario negri 2, 20156 Milano, Italy.

Department of Chemistry, Materials and Chemical engineering "Giulio Natta", Politecnico di Milano, via Mancinelli 7, 20131 Milano, Italy; Department of Engineering, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128 Roma, Italy.

出版信息

J Control Release. 2021 Feb 10;330:218-228. doi: 10.1016/j.jconrel.2020.12.006. Epub 2020 Dec 10.

DOI:10.1016/j.jconrel.2020.12.006
PMID:33309836
Abstract

Astrogliosis has a unique reaction during spinal cord damage, with helpful or adverse impacts on recovery. There is consequently a pressing need for treatment to target activated astrocytes and their unsafe response after injury to ensure some preservative effect during the progressive damage. We specifically developed and characterized a functionalized nanogel-based nanovector in vitro and in vivo, demonstrating its selectivity towards astrocytes, and limited uptake by macrophages when functionalized with both NH and Cy5 groups. In vitro experiments showed that the internalization was mediated by a clathrin-dependent endocytic pathway. After internalization into the cytoplasm of astrocytes, nanogels undergo lysosomal degradation and release compounds with potential therapeutic efficacy.

摘要

星形胶质细胞在脊髓损伤时有独特的反应,对恢复有有益或不利的影响。因此,迫切需要针对激活的星形胶质细胞及其损伤后的不安全反应进行治疗,以在进行性损伤过程中确保一定的保护作用。我们专门在体外和体内开发和表征了一种基于功能化纳米凝胶的纳米载体,证明了当同时用 NH 和 Cy5 基团功能化时,它对星形胶质细胞具有选择性,并且被巨噬细胞摄取的程度有限。体外实验表明,内吞作用是通过网格蛋白依赖性内吞途径介导的。纳米凝胶进入星形胶质细胞的细胞质后,会经历溶酶体降解,并释放具有潜在治疗效果的化合物。

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