Functionalized nanogel for treating activated astrocytes in spinal cord injury

• Published in: Journal of controlled release 2021-02, Vol.330, p.218-228
• Main Authors: Papa, Simonetta, Veneruso, Valeria, Mauri, Emanuele, Cremonesi, Giada, Mingaj, Xhuljana, Mariani, Alessandro, De Paola, Massimiliano, Rossetti, Arianna, Sacchetti, Alessandro, Rossi, Filippo, Forloni, Gianluigi, Veglianese, Pietro
• Format: Article
• Language: English
• Subjects: Astrocytes; Inflammation; Nanogel; Nanoparticles; Spinal cord injury
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2020.12.006

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 NH2 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. [Display omitted] •Targeting inflammation in spinal cord injury, a new strategy.•Nanogel-based nanovector is selective for astrocyte, limiting the phagocyte problem.•Nanogel-based nanovector releases compounds with therapeutic efficacy in astrocytes.•Rolipram is able to act on the astrogliosis in an in vivo SCI model.