Negrete, Maria , Romero-Ben, Elena , Gutierrez-Valencia, Alicia , Rosales-Barrios, Cristian , Ales, Eva , Mena-Barragan, Teresa , Flores, Juan A. , CASTILLEJOS ANGUIANO, MARIA DEL CARMEN, de la Cruz-Ojeda, Patricia , Navarro-Villaran, Elena , Cepeda-Franco, Carmen , Khiar, Noureddine , Muntane, Jordi
Si
ACS Appl. Bio Mater.
Article
Científica
0.746
21/06/2021
000664594300011
Hepatocellular carcinoma (HCC) is the sixth most common neoplasia and the fourth most common cause of cancer-related mortality worldwide. Sorafenib is the first-line molecular therapy for patients in an advanced stage of HCC. However, the recommended clinical dose of Sorafenib is associated with several complications, which derive from its lack of cell specificity and its very low water solubility. To circumvent these drawbacks, in the present study we developed two sugarcoated polydiacetylene-based nanomicelles-Sorafenib carriers targeting mannose and asialoglycoprotein receptors (MR and ASGPR, respectively). The strategies allowed the inducement of apoptosis and reduction of cell proliferation at a nanomolar, instead of micromolar, range in liver cancer cells. The study showed that, contrary to literature data, Sorafenib included into the pMicMan (Man = mannose) vector (targeting MR) is more efficient than pMicGal (Gal = galactose) (targeting ASGPR). Indeed, pMicMan increased the endosomal incorporation with an increased intracellular Sorafenib concentration that induced apoptosis and reduced cell proliferation at a low concentration range (10-20 nM).
active drug delivery; polydiacetylene-based nanomicelles; mannose receptor; asialoglycoprotein receptor; apoptosis; cell proliferation; cell trafficking; hepatocellular carcinoma