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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 sugar-coated 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).

In this study, a "click and hybridization" strategy was developed for the functionalization of polydiacetylene micelles with a targeting aptamer ligand. Decoration of the nanocarriers with an anti-Annexin A2 sequence efficiently triggered enhanced internalization of the functionalized micelles in the MCF-7 cell line, with a marked increase compared to control micelles., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Polydiacetylene-based nanoparticles have been developed as nanocarriers for various bio-applications. However, how nanocarriers enter the cell environment and affect cell viability has not yet been considerably explored. In this study, polydiacetylene-based nanoliposomes (nanosomes) were electrostatically complexed with rhodamine fluorophores. Based on real-time cell imaging and cell viability assessment, the most highly polymerized nanosomes were found to be less toxic to cells. Moreover, it was revealed that the rhodamine/polydiacetylene nanosome complex dissociates at cell environment, the polydiacetylene nanosome penetrates into cells, as suggested by the fluorescence observed in confocal microscopy images.