Vertaisarvioitu alkuperäisartikkeli tai data-artikkeli tieteellisessä aikakauslehdessä (A1)

Macrophage Hitchhiking Nanoparticles for the Treatment of Myocardial Infarction: An In Vitro and In Vivo Study




Julkaisun tekijätTorrieri Giulia, Iqbal Imran, Fontana Flavia, Talman Virpi, Liljenbäck Heidi, Putri Andriana, Nammas Wail, Rajander Johan, Guo-Li Xiang, Low Philip S., Teesalu Tambet, Roivainen Anne, Hirvonen Jouni, Ruskoaho Heikki, Balasubramanian Vimalkumar, Saraste Antti, Santos Hélder A.

Julkaisuvuosi2023

JournalAdvanced Functional Materials

eISSN1616-3028

DOIhttp://dx.doi.org/10.1002/adfm.202303658

Verkko-osoitehttps://onlinelibrary.wiley.com/doi/full/10.1002/adfm.202303658

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/179620917


Tiivistelmä

Myocardial infarction (MI) is the leading cause of death worldwide. However, current therapies are unable to restore the function of the injured myocardium. Advanced approaches, such as stimulation of cardiomyocyte (CM) proliferation are promising, but suffer from poor pharmacokinetics and possible systemic adverse effects. Nanomedicines can be a solution to the above-mentioned drawbacks. However, targeting the cardiac tissue still represents a challenge. Herein, a MI-selective precision nanosystem is developed, that relies on the heart targeting properties of atrial natriuretic peptide (ANP) and lin-TT1 peptide-mediated hitchhiking on M2-like macrophages. The system based on pH-responsive putrescine-modified acetalated dextran (Putre-AcDEX) nanoparticles, shows biocompatibility with cultured cardiac cells, and ANP receptor-dependent interaction with CMs. Moreover, treatment with nanoparticles (NPs) loaded with two pleiotropic cellular self-renewal promoting compounds, CHIR99021 and SB203580, induces a 4-fold increase in bromodeoxyuridine (BrdU) incorporation in primary cardiomyocytes compared to control. In vivo studies confirm that M2-like macrophages targeting by lin-TT1 peptide enhances the heart targeting of ANP. In addition, NP administration does not alter the immunological profile of blood and spleen, showing the short-term safety of the developed system in vivo. Overall, the study results in the development of a peptide-guided precision nanosystem for delivery of therapeutic compounds to the infarcted heart.


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Last updated on 2023-05-06 at 08:12