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).

BackgroundSuPAR 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.MethodsWe performed conventional and tissue Doppler echocardiography and measured plasma suPAR levels.ResultsWe 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).ConclusionWe demonstrate additional ability of suPAR, over age, to predict impaired myocardial relaxation.Trial registrationClinicalTrials.gov Identifier: NCT02791139 (Registered May 31, 2016).

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