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Schematic diagram of the myocardial infarction (MI) model using coronary artery embolism. (a) The puncture was performed at the obvious pulse location on the right femoral artery. (b) The artery sheath was inserted after puncture. (c) After the angiographic catheter reached the opening of the left coronary artery, the microguide wire and catheter could access the left anterior descending coronary artery. (d) The left coronary artery branches were clearly displayed before the MI modeling by coronary angiography. D1 = the first diagonal branch; D2 = the second diagonal branch; and D3 = the third diagonal branch. (e) After embolism of the coronary artery, the second diagonal branch distal of the left anterior descending artery was blocked. The second coronary angiography confirmed ischemia in the embolism area.
Source publication
Objective
This study aimed to develop a gene delivery system using ultrasound-targeted microbubbles destruction (UTMD) combined with nuclear localization signal (NLS) and investigate its efficacy and safety for therapeutic angiogenesis in canine myocardial infarction (MI) model.
Methods
Fifty MI dogs were randomly divided into 5 groups and transfe...
Citations
... In this way, they can favor angiogenesis [20], restore the presence of miR-21, which is essential for proper heart functioning [17], downregulate the expression of certain genes such as Gal-7 or (GSK)-3β genes to suppress a local immune response in the heart and hence allow heart grafting [17], or restore atherosclerotic plaque stability [52]. It has been suggested that the gene delivery method for the treatment of heart diseases such as myocardial infarction can be improved by combining UTMD with nuclear localization signal (NLS), which can facilitate DNA transfer from the cytoplasm to nucleus [53]. Through the activation of acidic fibroblast growth factor (FGF1 or aFGF-P), MBs can promote fibroblast development in cardiac tissue to prevent heart failure [18]. ...
A variety of different nanomaterials (NMs) such as microbubbles (MBs), nanobubbles (NBs), nanodroplets (NDs), and silica hollow meso-structures have been tested as ultrasound contrast agents for the detection of heart diseases. The inner part of these NMs is made gaseous to yield an ultrasound contrast, which arises from the difference in acoustic impedance between the interior and exterior of such a structure. Furthermore, to specifically achieve a contrast in the diseased heart region (DHR), NMs can be designed to target this region in essentially three different ways (i.e., passively when NMs are small enough to diffuse through the holes of the vessels supplying the DHR, actively by being associated with a ligand that recognizes a receptor of the DHR, or magnetically by applying a magnetic field orientated in the direction of the DHR on a NM responding to such stimulus). The localization and resolution of ultrasound imaging can be further improved by applying ultrasounds in the DHR, by increasing the ultrasound frequency, or by using harmonic, sub-harmonic, or super-resolution imaging. Local imaging can be achieved with other non-gaseous NMs of metallic composition (i.e., essentially made of Au) by using photoacoustic imaging, thus widening the range of NMs usable for cardiac applications. These contrast agents may also have a therapeutic efficacy by carrying/activating/releasing a heart disease drug, by triggering ultrasound targeted microbubble destruction or enhanced cavitation in the DHR, for example, resulting in thrombolysis or helping to prevent heart transplant rejection.
... Free diffusion through nuclear pores can occur for smaller nucleic acids (<40kDa), but larger molecules require nuclear localization signal (NLS) active transporters that are energy intensive [323,324]. Ultrasound-targeted microbubble destruction (UTMD) of the lipid and subsequent nuclear penetration continues to be a major issue affecting gene transfection bilayer membrane, a novel approach to permeabilize the membrane and enhance nucleic acid transport, releases energy into the cell [85] that could be used to power the NLS active transporters [325]. UTMD functions by utilizing ultrasound to collapse microbubbles, creating localized cavitation areas that form pores in the lipid bilayer of cells facilitating diffusive transport of large molecules, such as polypeptides and pDNA [326]. ...
... UTMD functions by utilizing ultrasound to collapse microbubbles, creating localized cavitation areas that form pores in the lipid bilayer of cells facilitating diffusive transport of large molecules, such as polypeptides and pDNA [326]. By conjugating NLS peptides to pDNA for angiopoietin 1, nuclear trafficking and uptake were significantly improved resulting in increased microvessel formation in canine hearts following MI [85]. ...
Cardiovascular disease is the leading cause of death around the world, in which myocardial infarction (MI) is a precipitating event. However, current therapies do not adequately address the multiple dysregulated systems following MI. Consequently, recent studies have developed novel biologic delivery systems to more effectively address these maladies. This review utilizes a scientometric summary of the recent literature to identify trends among biologic delivery systems designed to treat MI. Emphasis is placed on sustained or targeted release of biologics (e.g. growth factors, nucleic acids, stem cells, chemokines) from common delivery systems (e.g. microparticles, nanocarriers, injectable hydrogels, implantable patches). We also evaluate biologic delivery system trends in the entire regenerative medicine field to identify emerging approaches that may translate to the treatment of MI. Future developments include immune system targeting through soluble factor or chemokine delivery, and the development of advanced delivery systems that facilitate the synergistic delivery of biologics.
