Drug-loaded Multifunctional Nanoparticles Targeted to the Endocardial Layer of the Injured Heart Modulate Hypertrophic Signaling

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu


Ischemic heart disease is the leading cause of death globally. Severe myocardial ischemia results in a massive loss of myocytes and acute myocardial infarction, the endocardium being the most vulnerable region. At present, current therapeutic lines only ameliorate modestly the quality of life of these patients. Here, we report an engineered nanocarrier for targeted drug delivery into the
endocardial layer of the left ventricle for cardiac repair. Biodegradable porous silicon (PSi) nanoparticles were functionalized with atrial natriuretic peptide (ANP), which is known to be expressed predominantly in the endocardium of the failing heart. The ANP-PSi nanoparticles exhibit improved colloidal stability and enhanced cellular interactions with cardiomyocytes and non-myocytes with minimal toxicity. After confirmation of good retention of the radioisotope 111-Indium in relevant physiological buffers over 4 hours, in vivo SPECT/CT imaging and autoradiography demonstrate increased accumulation of ANP-PSi nanoparticles in the ischemic heart, particularly in the endocardial layer of the left ventricle. Moreover, ANP-PSi nanoparticles loaded with a novel cardioprotective small molecule attenuate hypertrophic signaling in the endocardium, demonstrating cardioprotective potential. These results provide unique insights into the development of nanotherapies targeted to the injured region of the myocardium.
DOI - pysyväislinkit
TilaJulkaistu - 6 syysk. 2017
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu


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