Nanoparticle delivery of cardioprotective therapies.

Acute myocardial infarction (AMI), and the heart failure (HF) that often follows, are leading causes of death and disability worldwide. Crucially, there are currently no effective treatments, other than myocardial reperfusion, for reducing myocardial infarct (MI) size and preventing HF following AMI. Thus, there is an unmet need to discover novel cardioprotective therapies to reduce MI size, and prevent HF in AMI patients. Although a large number of therapies have been shown to reduce MI size in experimental studies, the majority have failed to benefit AMI patients. Failure to deliver cardioprotective therapy to the ischemic heart in sufficient concentrations following AMI is a major factor for the lack of success observed in previous clinical cardioprotection studies. Therefore, new strategies are needed to improve the delivery of cardioprotective therapies to the ischemic heart following AMI. In this regard, nanoparticles have emerged as drug delivery systems for improving the bioavailability, delivery, and release of cardioprotective therapies, and should result in improved efficacy in terms of reducing MI size and preventing HF. In this article, we provide a review of currently available nanoparticles, some of which have been FDA-approved, in terms of their use as drug delivery systems in cardiovascular disease and cardioprotection.

Value of soluble Urokinase plasminogen activator receptor over age as a biomarker of impaired myocardial relaxation.

BACKGROUND: SuPAR is a biomarker that reflects the level of immune activation. As inflammation plays an important role in the ageing process of the cardiovascular system, we hypothesized that suPAR might be a useful predictive biomarker of the ageing heart. METHODS: We performed conventional and tissue Doppler echocardiography and measured plasma suPAR levels. RESULTS: We studied community adults (n=120, 37.5% female) (mean age: 70.3±9.3 years) without known cardiovascular disease (CVD). Participants with impaired myocardial relaxation were older (84% vs 59% were aged ≥71 years, p=0.002), with more diabetes mellitus (27% vs 11%, p=0.034). SuPAR levels were higher among participants with impaired myocardial relaxation (3.9 ng/ml vs 3.0 ng/ml, p=0.015). At the univariate level, older age (OR 3.6; 95%CI 1.6, 8.5; p=0.003), diabetes mellitus (OR 3.04; 95%CI 1.1, 8.8; p=0.04), systolic blood pressure (OR 1.03; 95%CI 1.001, 1.1; p=0.041) and suPAR levels ≥3.00ng/ml (OR 3.4; 95%CI 1.16, 7.4; p=0.002) were associated with impaired myocardial relaxation. In multivariable regression analysis, only older age (OR 2.8; 95%CI 1.1, 6.7; p=0.026) and suPAR (OR 2.7; 95%CI 1.2, 6.1; p=0.018) remained independently associated with impaired myocardial relaxation. Receiver operating characteristics (ROC) curve analysis revealed an area under the curve (AUC) value of 0.63 (95% CI 0.54, 0.71) for model that included age alone. Addition of suPAR significantly increased AUC value to 0.70 (95%CI 0.60, 0.79), which was significantly larger than the model with age alone (p=0.016). CONCLUSION: We demonstrate additional ability of suPAR, over age, to predict impaired myocardial relaxation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02791139 (Registered May 31, 2016).

Hydroxyapatite-intertwined hybrid nanofibres for the mineralization of osteoblasts.

Advances in tissue engineering have enabled the development of bioactive composite materials to generate biomimetic nanofibrous scaffolds for bone replacement therapies. Polymeric biocomposite nanofibrous scaffolds architecturally mimic the native extracellular matrix (ECM), delivering tremendous regenerative potential for bone tissue engineering. In the present study, biocompatible poly(l-lactic acid)-co-poly(ε-caprolactone)-silk fibroin-hydroxyapatite-hyaluronic acid (PLACL-SF-HaP-HA) nanofibrous scaffolds were fabricated by electrospinning to mimic the native ECM. The developed nanofibrous scaffolds were characterized in terms of fibre morphology, functional group, hydrophilicity and mechanical strength, using SEM, FTIR, contact angle and tabletop tensile-tester, respectively. The nanofibrous scaffolds showed a higher level of pore size and increased porosity of up to 95% for the exchange of nutrients and metabolic wastes. The fibre diameters obtained were in the range of around 255 ± 13.4-789 ± 22.41 nm. Osteoblasts cultured on PLACL-SF-HaP-HA showed a significantly (p < 0.001) higher level of proliferation (53%) and increased osteogenic differentiation and mineralization (63%) for the inclusion of bioactive molecules SF-HA. Energy-dispersive X-ray analysis (EDX) data proved that the presence of calcium and phosphorous in PLACL-SF-HaP-HA nanofibrous scaffolds was greater than in the other nanofibrous scaffolds with cultured osteoblasts. The obtained results for functionalized PLACL-SF-HaP-HA nanofibrous scaffolds proved them to be a potential biocomposite for bone tissue engineering. Copyright © 2015 John Wiley & Sons, Ltd.

NIR photoresponsive crosslinked upconverting nanocarriers toward selective intracellular drug release.

An NIR-responsive mesoporous silica coated upconverting nanoparticle (UCNP) conjugate is developed for controllable drug delivery and fluorescence imaging in living cells. In this work, antitumor drug doxorubicin (Dox) molecules are encapsulated within cross-linked photocaged mesoporous silica coated UCNPs. Upon 980 nm light irradiation, Dox could be selectively released through the photocleavage of theo-nitrobenzyl (NB) caged linker by the converted UV emission from UCNPs. This NIR light-responsive nanoparticle conjugate demonstrates high efficiency for the controlled release of the drug in cancer cells. Upon functionalization of the nanocarrier with folic acid (FA), this photocaged FA-conjugated silica-UCNP nanocarrier will also allow targeted intracellular drug delivery and selective fluorescence imaging towards the cell lines with high level expression of folate receptor (FR).