In vitro and in vivo assessment of heart-homing porous silicon nanoparticles

Ferreira, Mónica P. A.; Ranjan, Sanjeev; Correia, Alexandra; Mäkilä, Ermei; Kinnunen, Sini; Zhang, Hongbo; Shahbazi, Mohammad‐Ali; Almeida, Patrick; Salonen, Jarno; Ruskoaho, Heikki; Airaksinen, Anu J.; Hirvonen, Jouni; Santos, Hélder A.

doi:10.1016/j.biomaterials.2016.03.046

Cited by 72 publications

(46 citation statements)

References 67 publications

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“…In order to clarify whether the ANP‐modified nanoparticles were interacting with cardiac cells via the NPRs, the cardiomyocytes and non‐myocytes with free ANP peptide and the Un‐P‐D‐ANP nanoparticles were incubated. In agreement with our previous observations, the presence of free ANP peptide decreased the cellular internalization of Un‐P‐D‐ANP nanoparticles in cardiomyocytes in a concentration‐dependent manner (Figure e). The same attenuation of the internalization was found in non‐myocyte cells (Figure j), in agreement with reports on the ANP–NPR specific interactions .…”

Section: Resultssupporting

confidence: 93%

“…The ATR–FTIR spectroscopy showed attenuation of the carbonyl CO stretching band at 1716 cm −1 after covalent attachment of polyethylene glycol (PEG) to the UnTHCPSi nanoparticles and formation of amides I and II (1635 cm −1 , CO stretching for amide I, shoulder at 1532 cm −1 as the in‐plane NH bending and CN stretching for amide II). Covalent addition of S‐2‐(4‐aminobenzil)‐1, 4, 7, 10‐tetraazacyclododecane‐1,4,7,10‐tetrater‐butyl acetate (DOTA) (Un‐P‐D) caused a prominent band at 1716 cm −1 due to the free CO 2 H groups . The formation of the amide I and II bands and a broad band at 3278 cm −1 (NH stretching vibration) was characteristic for the Un‐P‐D‐ANP nanoparticles as a result of the covalent binding of ANP on the nanoparticle surface (Figure S2, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

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Drug‐Loaded Multifunctional Nanoparticles Targeted to the Endocardial Layer of the Injured Heart Modulate Hypertrophic Signaling

Ferreira

Ranjan

Kinnunen

et al. 2017

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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, an engineered nanocarrier is reported for targeted drug delivery into the endocardial layer of the left ventricle for cardiac repair. Biodegradable porous silicon (PSi) nanoparticles are 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 h, in vivo single-photon emission computed tomography (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.

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Section: Resultssupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Drug‐Loaded Multifunctional Nanoparticles Targeted to the Endocardial Layer of the Injured Heart Modulate Hypertrophic Signaling

Ferreira

Ranjan

Kinnunen

et al. 2017

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“…This endothelialized-myocardium-on-a-chip platform would also enable testing of nanomedicine [4,5,83,84], such as the interactions between nanoparticles and the cardiac cells [85–87] as well as those between nanoparticles and the endothelium ( e.g . nanoparticle-induced endothelial leakage, a non-toxic effect of nanoparticles on endothelial cells [31,88]).…”

Section: Discussionmentioning

confidence: 99%

Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip

et al. 2016

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Engineering cardiac tissues and organ models remains a great challenge due to the hierarchical structure of the native myocardium. The need of integrating blood vessels brings additional complexity, limiting the available approaches that are suitable to produce integrated cardiovascular organoids. In this work we propose a novel hybrid strategy based on 3D bioprinting, to fabricate endothelialized myocardium. Enabled by the use of our composite bioink, endothelial cells directly bioprinted within microfibrous hydrogel scaffolds gradually migrated towards the peripheries of the microfibers to form a layer of confluent endothelium. Together with controlled anisotropy, this 3D endothelial bed was then seeded with cardiomyocytes to generate aligned myocardium capable of spontaneous and synchronous contraction. We further embedded the organoids into a specially designed microfluidic perfusion bioreactor to complete the endothelialized-myocardium-on-a-chip platform for cardiovascular toxicity evaluation. Finally, we demonstrated that such a technique could be translated to human cardiomyocytes derived from induced pluripotent stem cells to construct endothelialized human myocardium. We believe that our method for generation of endothelialized organoids fabricated through an innovative 3D bioprinting technology may find widespread applications in regenerative medicine, drug screening, and potentially disease modeling.

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“…Histological evaluation of the liver sections revealed that the nanoparticles were located mainly in the lumen of the liver blood vessels and were able to emanate also into the sinusoids. A more successful example on improving PSi blood‐circulation time by PEGylation can be presented by comparing two separate studies in which heart‐targeting atrial natriuretic peptide (ANP) functionalized UnTHCPSi NPs were investigated by using 111 In‐labeled NPs and SPECT/CT imaging . The biodistribution of the ANP‐modified PEGylated (Un‐P‐D‐ANP) and non‐PEGylated [ 111 In]UnTHCPSi NPs was monitored in a rat model of heart ischemia, which had been induced by an isoprenaline injection 24 h prior to the experiment.…”

Section: In Vivo Imaging With Silicon‐based Materialsmentioning

confidence: 99%

Multimodality Imaging of Silica and Silicon Materials In Vivo

et al. 2018

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Recent progress in the development of silica- and silicon-based multimodality imaging nanoprobes has advanced their use in image-guided drug delivery, and the development of novel systems for nanotheranostic and diagnostic applications. As biocompatible and flexibly tunable materials, silica and silicon provide excellent platforms with high clinical potential in nanotheranostic and diagnostic probes with well-defined morphology and surface chemistry, yielding multifunctional properties. In vivo imaging is of great value in the exploration of methods for improving site-specific nanotherapeutic delivery by silica- and silicon-based drug-delivery systems. Multimodality approaches are essential for understanding the biological interactions of nanotherapeutics in the physiological environment in vivo. The aim here is to describe recent advances in the development of in vivo imaging tools based on nanostructured silica and silicon, and their applications in single and multimodality imaging.

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In vitro and in vivo assessment of heart-homing porous silicon nanoparticles

Cited by 72 publications

References 67 publications

Drug‐Loaded Multifunctional Nanoparticles Targeted to the Endocardial Layer of the Injured Heart Modulate Hypertrophic Signaling

Drug‐Loaded Multifunctional Nanoparticles Targeted to the Endocardial Layer of the Injured Heart Modulate Hypertrophic Signaling

Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip

Multimodality Imaging of Silica and Silicon Materials In Vivo

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