Dual‐drug delivery using dextran‐functionalized nanoparticles targeting cardiac fibroblasts for cellular reprogramming

Mónica P. A. Ferreira*, Virpi Talman, Giulia Torrieri, Dongfei Liu, Gonçalo Marques, Karina Moslova, Zehua Liu, João F. Pinto, Jouni Hirvonen, Heikki Ruskoaho, Hélder A. Santos

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

59 Citaten (Scopus)


The inability of the heart to recover from an ischemic insult leads to the formation of fibrotic scar tissue and heart failure. From the therapeutic strategies under investigation, cardiac regeneration holds the promise of restoring the full functionality of a damaged heart. Taking into consideration the presence of vast numbers of fibroblasts and myofibroblasts in the injured heart, direct fibroblast reprogramming into cardiomyocytes using small drug molecules is an attractive therapeutic option to replenish the lost cardiomyocytes. Here, a spermine-acetalated dextran-based functional nanoparticle is developed for pH-triggered drug delivery of two poorly water soluble small molecules, CHIR99021 and SB431542, both capable of increasing the efficiency of direct reprogramming of fibroblast into cardiomyocytes. Upon functionalization with polyethylene glycol and atrial natriuretic peptide, the biocompatibility of the nanosystem is improved, and the cellular interactions with the cardiac nonmyocytes are specifically augmented. The dual delivery of the compounds is verified in vitro, and the compounds exerted concomitantly anticipate biological effects by stabilizing β-catenin (CHIR99021) and by preventing translocation of Smad3 to the nucleus of (myo)fibroblasts (SB431542). These observations highlight the potential of this nanoparticle-based system toward improved drug delivery and efficient direct reprogramming of fibroblasts into cardiomyocyte-like cells, and thus, potential cardiac regeneration therapy.
Originele taal-2English
Aantal pagina's12
TijdschriftAdvanced Functional Materials
Nummer van het tijdschrift15
StatusPublished - 11-apr.-2018
Extern gepubliceerdJa

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