A targeted polypeptide-based nanoconjugate as a nanotherapeutic for alcohol-induced neuroinflammation.

Autores de CIPF

• Carlos Manuel Cuesta Díaz

  Autor

• Francesc Ibáñez Cabanes

  Autor

• Rosa López Hidalgo

  Autor

• Juan Ramon Ureña Peralta

  Autor

• 

  Ana Armiñan De Benito

  Autor

• 

  Maria Jesus Vicent Docon

  Autor

• Maria Pascual Mora

  Autor

• Consuelo Guerri Sirera

  Autor

Participantes ajenos a CIPF

• Duro-Castano, Aroa

Grupos de Investigación

• Laboratorio de Polímeros Terapéuticos

  

  Jefe/a de Grupo

  Maria Jesus Vicent Docon

Abstract

Alcohol abuse induces the expression of inflammatory mediators by activating the immune receptors to trigger neuroinflammation and brain damage; however, therapies that reduce neuroimmune system activation may protect against alcohol's damaging effects. Curcuminoids possess anti-inflammatory properties but suffer from low bioavailability; therefore, we designed a new receptor-targeted biodegradable star-shaped crosslinked polypeptide polymer that bears propargylamine moieties and bisdemethoxycurcumin (StClPr-BDMC-ANG) as an enhanced anti-inflammatory therapeutic that penetrates the blood-brain-barrier and ameliorates alcohol-induced neuroinflammation. StClPr-BDMC-ANG administration maintains the viability of primary glia and inhibits the ethanol-induced upregulation of crucial inflammatory mediators in the prefrontal and medial cortex in a mouse model of chronic ethanol consumption. StClPr-BDMC-ANG treatment also suppresses the ethanol-mediated downregulation of microRNAs known to negatively modulate neuroinflammation in the brain cortex (miRs 146a-5p and let-7b-5p). In summary, our results demonstrate the attenuation of alcohol-induced neuroinflammation by an optimized and targeted polypeptide-based nanoconjugate of a curcuminoid.

Keywords

• Polypeptides; Polymer-drug conjugates; Alcohol-induced neuroinflammation; Curcuminoids; miRNA