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In Vitro Evaluation of the Therapeutic Effects of Dual‐Drug Loaded Spermine‐Acetalated Dextran Nanoparticles Coated with Tannic Acid for Cardiac Applications
Author(s) -
Torrieri Giulia,
Ferreira Mónica P. A.,
Shahbazi MohammadAli,
Talman Virpi,
Karhu S. Tuuli,
Pohjolainen Lotta,
Carvalho Cláudia,
Pinto João F.,
Hirvonen Jouni,
Ruskoaho Heikki,
Balasubramanian Vimalkumar,
Santos Hélder A.
Publication year - 2022
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.202109032
Subject(s) - tannic acid , biocompatibility , spermine , materials science , extracellular matrix , in vivo , cell growth , in vitro , nanocarriers , osteopontin , biomedical engineering , microbiology and biotechnology , drug delivery , nanotechnology , biochemistry , chemistry , biology , medicine , immunology , organic chemistry , metallurgy , enzyme
Myocardial infarction results in a massive loss of cardiomyocytes (CMs). Unfortunately, current therapies are unsuccessful in replacing lost CMs, and thus, there is an urgent need for innovative approaches. Here, a nanosystem based on spermine‐acetalated dextran (AcDXSp) and encapsulating two drug compounds able to stimulate in vitro CMs proliferation is developed. The nanosystem is coated by deposition of a film constituted by tannic acid (TA) and Fe 3+ ions. The coating with TA increases the retention of the nanocarrier in cell co‐cultures of CMs and fibroblasts stimulated with transforming growth factor (TGF)‐β, due to the high affinity of TA for components of the cardiac extracellular matrix. The system exhibits biocompatibility toward primary CMs and induces their proliferation, as indicated by the two‐fold increase of CMs in the active cell cycle. At the same time, the presence of TA synergistically helps contrasting fibrosis by reducing profibrotic genes expression, such as collagen 1 and osteopontin, by approximately 80% compared to the control. Overall, the developed nanosystem demonstrates the capability to stimulate CMs proliferation and reduce fibrosis, showing potential benefits for future in vivo applications.