Development of a highly selective and sensitive imaging probe for accurate detection of myocardial hypoxia will be helpful to estimate the degree of ischemia and subsequently guide personalized treatment. However, an efficient optical approach for hypoxia monitoring in myocardial ischemia is still lacking. In this work, a cardiomyocyte-specific and nitroreductase-activatable nearinfrared nanoprobe has been developed for selective and sensitive imaging of myocardial hypoxia. The nanoprobe is a liposome-based nanoarchitecture which is functionalized with a peptide (GGGGDRVYIHPF) for targeting heart cells and encapsulating a nitrobenzene-substituted BODIPY for nitroreductase imaging. The nanoprobe can specifically recognize and bind to angiotensin II type 1 receptor that is overexpressed on the ischemic heart cells by the peptide and is subsequently uptaken into heart cells, in which the probe is released and activated by hypoxia-related nitroreductase to produce fluorescence emission at 713 nm. The in vitro response of the nanoprobe toward nitroreductase resulted in 55-fold fluorescence enhancement with the limit of detection as low as 7.08 ng/mL. Confocal fluorescence imaging confirmed the successful uptake of nanoprobe by hypoxic heart cells and intracellular detection of nitroreductase. More significantly, in vivo imaging of hypoxia in a murine model of myocardial ischemia was achieved by the nanoprobe with high sensitivity and good biocompatibility. Therefore, this work presents a new tool for targeted detection of myocardial hypoxia and will promote the investigation of the hypoxia-related physiological and pathological process of ischemic heart disease.
Rationale: Despite considerable advances, the reactive oxygen species (ROS)-mediated cancer treatment suffers from the problems of up-regulation of adaptive antioxidants in cancer cells as well as side effects to normal cells. Therefore, development of a new generation of cancer-specific nanomedicine capable of amplifying oxidative stress would be of great interest for accurate and effective cancer treatment.Methods: Herein, transferrin (Tf)-decorated, dihydroartemisinin (DHA), L-buthionine-sulfoximine (BSO), and CellROX-loaded liposomal nanoparticles (Tf-DBC NPs) were developed for precise cancer theranositcs. Tf-DBC NPs could specifically recognize cancer cells via Tf-Tf receptor binding and be uptaken into the lysosomes of cancer cells, where Tf-DBC NPs were activated to release Fe(II), DHA, and BSO. ROS was generated by DHA in the presence of Fe(II), and GSH was depleted by BSO to disrupt the redox balance in cancer cells. Furthermore, CellROX, as a fluorescent probe for imaging of intracellular oxidative stress, was used to monitor the therapeutic efficacy.Results: The integration of Tf, DHA, and BSO into the acidic pH-responsive liposomes selectively and effectively killed cancer cells and prevented the oxidative injury to normal cells. The high oxidative state was visualized at the tumor site and the amplification of oxidative stress enabled tumor eradication by Tf-DBC NPs, demonstrating the successful implementation of this novel strategy in vivo.Conclusion: Our study provides a new paradigm for the design of ROS-mediated therapeutics and offers a promising perspective for precise cancer treatment.
Matrix
metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2
(MMP-2) play important roles in the progression of renal interstitial
fibrosis (RIF). There is an increasing demand to construct a novel
method for the simultaneous detection of MMP-9 and MMP-2 to monitor
the progression of RIF. Herein, a strategy based on the nanoplatform
composed of the polydopamine nanosphere and fluorescence-labeled aptamers
is developed to simultaneously detect MMP-9 and MMP-2 with DNase-I-assisted
recycling signal amplification. In the light of tracing the recovered
fluorescence intensity at 520 and 610 nm upon adding MMP-9 and MMP-2,
the increased fluorescence intensity is linear to the different concentrations
of MMP-9 and MMP-2 with the detection limits of 9.6 and 25.6 pg/mL
for MMP-9 and MMP-2, respectively. More intriguingly, the results
of unilateral ureteral obstruction mice show that the concentration
of MMP-9 in urine is increased with the extension of ligation time
while the concentration of MMP-2 is reversed, indicating that the
ratio of MMP-9 to MMP-2 could be considered as the potential urinary
biomarker to evaluate the progress of RIF and the therapeutic effect
of Huangkui capsule on RIF. Therefore, this study provides a paradigmatic
strategy for the simultaneous detection of the dual markers of RIF,
which is promising for the auxiliary clinical diagnosis and assessment
of the prognosis of chronic kidney disease.
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