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Mediated guidance of CaP to the heart

Mediated guidance of CaP to the heart

CUPIDO since its beginning has worked to develop synergistic targeting techniques that could maximize nanoparticle delivery to the heart. One of the options considered by the project is the functionalization of the CaP nanoparticles with aptamers, which should enhance the internalization into myocardial cells (http://www.cupidoproject.eu/guidance-to-the-heart/) Aptamers, short single stranded synthetic oligonucleotide, can fold into complex tertiary structures and thus are able to bind with high affinity to a specific target receptor on the surface of the target cells. Furthermore, compared to other targeting ligands and monoclonal antibodies, they show many additional advantages, such as low toxicity, high specificity, and superior stability in biological fluids. Based on these premises, in CUPIDO we first, generated a novel internalizing aptamer targeting cardiac cells, and then we efficiently functionalized the surface of the CaP…
Therapeutic efficacy of the ultimate formulation of Cupido nanoparticles

Therapeutic efficacy of the ultimate formulation of Cupido nanoparticles

Cupido’s partner CNR, Finceramica and Plumestars have closely collaborated during this period to establish the first proof of concept of the therapeutic efficacy of the ultimate formulation of Cupido nanoparticles: a dry powder of Calcium-Phosphate nanoparticle (dpCaPs) loaded with a known therapeutic molecule. The tests have been performed on mice with a specific cardiac disease and their heart activity has been monitored by a non-invasive technique: echocardiography, which uses sound waves to produce live images of the heart and its valves. Furthermore, the ultimate dpCaP formulation was administered via inhalation by a custom-made inhaler for small animals, which was generated and developed exclusively for CUPIDO. The first prototype of such a dry powder inhaler was improved based on the feedback collected in the first test campaign. The updated inhaler is…
Biodistribution in vivo

Biodistribution in vivo

The CUPIDO final product owns a certain technological complexity because it consists of two parts: the calcium phosphate nanoparticles that act as nano-carrier and the cardiac-specific drug, which needs to be encapsulated inside the nanoparticles. To dissect the biodistribution of each component, in Cupido we decided to first assess the features of each component and later to assess the biodistribution of the full loaded-nanoparticle to ensure that it is the whole product that is able to reach the heart. Regarding the carrier, the biodistribution of the CaPs nanocarrier has been studied in-vivo up to large animals: in Landrace pigs, three hundred minutes after inhalation of CaP nanoparticles loaded with a marker peptide, a signal was detected in the myocardium, providing evidence for effective delivery of the cargo to the heart…
Modelling perfusion in the human heart

Modelling perfusion in the human heart

Heart tissue is perfused by thousands of very small arteries and capillaries branching off the coronary arteries. Obtaining truthful representations of the exact geometries of the perfusion circulation using state-of-the-art imaging techniques is virtually impossible. Despite being the most fundamental process in maintaining organ health and the major pathway for drug delivery, perfusion has, from a computational point of view, received very little attention. Thanks to the work done by SIMULA in CUPIDO, a computationally efficient and accurate model is now available and provides a framework for the simulation of experimentally relevant time frames for pre-clinical research. In CUPIDO, SIMULA has developed a novel particle tracking-based method to simulate the distribution of nanoparticles in the heart mediated by perfusion. To model blood flow through perfused tissue they follow the approach…
Imaging of the nanoparticle’s distribution in animal models

Imaging of the nanoparticle’s distribution in animal models

One of the key issues in CUPIDO is to track where and when the inhaled CaP nanoparticles travel in the body in vivo (biodistribution). As a first approach, the imaging studies, performed by our partner BIOEMTECH, has been focused on the spatio-temporal biodistribution of the unloaded nanoparticles (without the drug) in mice, in particular in lungs, heart, intestine and kidneys. Nanoparticles have been labelled with technetium-99m (99mTc), the most common medical radioisotope used in clinical practice, that allows to track the signal of the nanoparticles inside the body through real-time, dynamic scintigraphy and/or tomography. Thanks to a new protocol, the incorporation of radioisotope in the nanoparticles is very high; furthermore, the size and physicochemical properties of the CaP nanoparticles aren’t altered. The stability of the technetium-99m attached to the nanoparticles…
A dedicated wearable device for minipigs

A dedicated wearable device for minipigs

In CUPIDO, the formulation developed within the project shall be tested for pre-clinical efficacy in large animals. As such, mini pigs are used to test first, i) if the inhaled nanoparticles show sufficient cardiac enrichment and then ii) if the drug-loaded nanoparticles restore the normal cardiac activity in a model of systolic heart failure (heart failure with reduced ejection fraction or HFrEF). All the tests are conducted at the facility of Charité – University Medicine Berlin, while the company LIFE designed and developed a dedicated wearable device to non-invasively measure several physiological parameters on mini-pigs. Partners at Charité and LIFE worked closely to understand the usage scenario and the functional requirements for the device. Together, they have already performed the early tests and the official evaluation of the measurements on…
CUPIDO at European Researchers’ Night

CUPIDO at European Researchers’ Night

The past weekend took place the European Researchers’ Nights: a large program of public events that bring researchers closer to the public. The events promote how researchers contribute to our society by displaying their work in an interactive and engaging forum. CUPIDO couldn't miss the chance to take part in this initiative and promote the work done by our team to develop inhalable nanoparticles that bring a drug to the heart. On Saturday 29th of September, the team of CNR-IRGB / Humanitas Research Hospital was at the science fair organized in Milan by the project MeetMeTonight (http://www.meetmetonight.it/milano/), where they engage the public in the journey of the nanoparticles through the body. The wonder that CUPIDO inspires in people is such a motivation booster!
A lightspot for CUPIDO at the European Society of Cardiology Congress 2019

A lightspot for CUPIDO at the European Society of Cardiology Congress 2019

This year CUPIDO arouse interest during the European Society of Cardiology Congress, one of the world’s largest and most influential cardiovascular event contributing to global awareness of the latest clinical trials and breakthrough discoveries. ESC Congress 2019 took place 31 August to 4 September at the Paris Expo Porte de Versailles, Paris - France. Our project coordinator Daniele Catalucci and a representative of our pharma partner SANOFI, were there to present the innovative delivery system to the heart that CUPIDO is developing.  Dr. Catalucci presented the latest results showing that a novel inhaled miR-133-loaded nanoparticle delivery approach can prevent cardiac dysfunction in an experimental model (Abstract 3072). The presentation of Daniele was first highlighted in the Daily Science News distributed to all the participants (available online too), and it was also…
Best Poster Award at the Conference of the European Society for Biomaterials

Best Poster Award at the Conference of the European Society for Biomaterials

Our partner Lorenzo deli Esposti, PhD student at the ISTEC-CNR, won the best poster award at the 30th Annual Conference of the European Society for Biomaterials,  held from September 9 to 13, in Dresden, Germany. The conference covered all aspects of biomaterial research and Lorenzo was there to present his latest results with the innovative biocompatible and biodegradable nanoparticles developed within Cupido. The presented results demonstrate that the inhalation of small (<50 nm in diameter)  calcium phosphate nanoparticles (CaPs) allows for their rapid translocation from the pulmonary tree to the bloodstream and to the heart, where their drug-cargo is quickly released. The poster won under the category Young Scientists  -  congratulation to Lorenzo for this achievement!  
Cardiovascular nanomedicine: the route ahead

Cardiovascular nanomedicine: the route ahead

What does the future hold for cardiovascular nanomedicine? The Journal of Nanomedicine asked our CUPIDO scientists to share their view on the topic in an editorial article. Cover of the Journal of Nanomedicine featuring the article. As they noticed, there is a huge gap in this area of medicine for novel therapeutics for improved patient outcomes. Nanotechnology may provide a solution to more effective treatment of disease, with better prognoses and a reduced side effect profile. In the review, the authors explore potential solutions to the limited pharmacological therapies currently on the market and the future that lies ahead for the place of nanotechnology within cardiovascular medicine. Indeed, while application of nanomedicine in patients afflicted by cardiovascular diseases is still in its infancy; as CUPIDO demonstrates, biocompatible and biodegradable nanoparticles…
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