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

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Abstract

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.
Original languageEnglish
Article number1701276
JournalSmall
Volume13
Issue number33
Number of pages14
ISSN1613-6829
DOIs
Publication statusPublished - 6 Sep 2017
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 116 Chemical sciences
  • 317 Pharmacy

Cite this

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title = "Drug-loaded Multifunctional Nanoparticles Targeted to the Endocardial Layer of the Injured Heart Modulate Hypertrophic Signaling",
abstract = "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.",
keywords = "116 Chemical sciences, 317 Pharmacy",
author = "Ferreira, {Monica P. A.} and Sanjeev Ranjan and Sini Kinnunen and Alexandra Correia and Virpi Talman and Ermei M{\"a}kil{\"a} and Brianda Barrios-Lopez and Marianna Kemell and Vimalkumar Balasubramanian and Jarno Salonen and Jouni Hirvonen and Heikki Ruskoaho and Airaksinen, {Anu J.} and Santos, {Helder A.}",
year = "2017",
month = "9",
day = "6",
doi = "10.1002/smll.201701276",
language = "English",
volume = "13",
journal = "Small",
issn = "1613-6810",
publisher = "Wiley-VCH",
number = "33",

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T1 - Drug-loaded Multifunctional Nanoparticles Targeted to the Endocardial Layer of the Injured Heart Modulate Hypertrophic Signaling

AU - Ferreira, Monica P. A.

AU - Ranjan, Sanjeev

AU - Kinnunen, Sini

AU - Correia, Alexandra

AU - Talman, Virpi

AU - Mäkilä, Ermei

AU - Barrios-Lopez, Brianda

AU - Kemell, Marianna

AU - Balasubramanian, Vimalkumar

AU - Salonen, Jarno

AU - Hirvonen, Jouni

AU - Ruskoaho, Heikki

AU - Airaksinen, Anu J.

AU - Santos, Helder A.

PY - 2017/9/6

Y1 - 2017/9/6

N2 - 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.

AB - 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.

KW - 116 Chemical sciences

KW - 317 Pharmacy

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DO - 10.1002/smll.201701276

M3 - Article

VL - 13

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JF - Small

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