Abstract
Restricted and controlled drug delivery to the heart remains a challenge giving frequent off-target effects as well as limited retention of drugs in the heart. There is a need to develop and optimize tools to allow for improved design of drug candidates for treatment of heart diseases. Over the last decade, novel drug platforms and nanomaterials were designed to confine bioactive materials to the heart. Yet, the research remains in its infancy, not only in the development of tools but also in the understanding of effects of these materials on cardiac function and tissue integrity. Upconverting nanoparticles are nanomaterials that recently accelerated interest in theranostic nanomedicine technologies. Their unique photophysical properties allow for sensitive in vivo imaging that can be combined with spatio-temporal control for targeted release of encapsulated drugs.Here we synthesized upconverting NaYF4:Yb,Tm nanoparticles and show for the first time their innocuity in the heart, when injected in the myocardium or in the pericardial space in mice. Nanoparticle retention and upconversion in the cardiac region did not alter heart rate variability, nor cardiac function as determined over a 15-day time course ensuing the sole injection. Altogether, our nanoparticles show innocuity primarily in the pericardial region and can be safely used for controlled spatiotemporal drug delivery. Our results support the use of upconverting nanoparticles as potential theranostics tools overcoming some of the key limitations associated with conventional experimental cardiology.
Highlights
Cardiovascular diseases (CVD), an umbrella term for a number of different pathologies including arteriosclerosis, coronary artery disease, arrhythmia, hypertension and heart failure, are the leading cause of morbidity and mortality in the world[1]
We examined heart rate (HR), as determined by real-time electrocardiogram (ECG) monitoring, during the excitation upconversion phase that was repeated throughout the entire time course, to identify whether the upconverting nanoparticles (UCNPs) and or the laser beam localized to the chest area, have an impact on cardiac rhythm
In an effort to identify the potential application of these UCNPs for heart specific photodynamic imaging, we decided to target the nanoparticles to the myocardium and/or the pericardial space
Summary
Cardiovascular diseases (CVD), an umbrella term for a number of different pathologies including arteriosclerosis, coronary artery disease, arrhythmia, hypertension and heart failure, are the leading cause of morbidity and mortality in the world[1]. Drug vectorization to the heart can be achieved by injection into the pericardial space which has a large potential for localized drug delivery [7]. Both approaches for injection, whether in the intramyocardial (intraMY) and intrapericardial (intraPE) space, are used in experimental and clinical settings and are highly adaptable to the study design and expected endpoints. Despite significant advances in the development of effective cardiac therapeutic agents and in drug delivery technologies, enduring drug availability in the heart remains a complex and pervasive conundrum in research and clinical settings. There is a need to develop drug-delivery and repeat-release approaches to deliver and maintain therapeutic materials to cardiac tissue with minimal adverse effects
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
