Theranostics
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Cyclooxygenase type 2 (COX-2) plays a predominant role in the progression of kidney injury in obstructive nephropathy. The aim of this study was to test the efficacy of chitosan/small interfering RNA (siRNA) nanoparticles to knockdown COX-2 specifically in macrophages to prevent kidney injury induced by unilateral ureteral obstruction (UUO). Using optical imaging techniques and confocal microscopy, we demonstrated that chitosan/siRNA nanoparticles accumulated in macrophages in the obstructed kidney. ⋯ Parenchymal inflammation, assessed by tumor necrosis factor-alpha (TNF-α) and interleukin 6 mRNA expression, was attenuated by COX-2 siRNA. Furthermore, treatment with COX-2 siRNA reduced heme oxygenase-1 and cleaved caspase-3 in UUO mice, indicating lesser oxidative stress and apoptosis. Our results demonstrate a novel strategy to prevent UUO-induced kidney damage by using chitosan/siRNA nanoparticles to knockdown COX-2 specifically in macrophages.
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The blood-brain barrier (BBB) can be transiently and locally opened by focused ultrasound (FUS) in the presence of microbubbles (MBs). Various imaging modalities and contrast agents have been used to monitor this process. Unfortunately, direct ultrasound imaging of BBB opening with MBs as contrast agent is not feasible, due to the inability of MBs to penetrate brain parenchyma. ⋯ Our results showed that the scale and distribution of FUS-induced BBB opening could be determined at high resolution by ultrasound perfusion kinetic analysis. The accuracy and sensitivity of this approach was validated by dynamic contrast-enhanced MRI. Our successful demonstration of ultrasound imaging to monitor FUS-induced BBB opening provides a new approach to assess FUS-dependent brain drug delivery, with the benefit of high temporal resolution and convenient integration with the FUS device.
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Review
CXCR4/CXCL12 axis in non small cell lung cancer (NSCLC) pathologic roles and therapeutic potential.
Lung cancer is the second most common malignancy and the leading cause of cancer-related death in the western world. Moreover, despite advances in surgery, chemotherapy and radiotherapy, the death rate from lung cancer remains high and the reported overall five-year survival rate is only 15%. Thus, novel treatments for this devastating disease are urgently needed. ⋯ Among the 19 chemokine receptors, CXCR4 is the receptor most widely expressed by malignant tumors and whose role in tumor biology is most thoroughly studied. The chemokine CXCL12, which is the sole ligand of CXCR4, is highly expressed in primary lung cancer as well as in the bone marrow, liver, adrenal glands and brain, which are all sites for lung cancer metastasis. This review focuses on the pathologic role of the CXCR4/CXCL12 axis in NSCLC and on the potential therapeutic implication of targeting this axis for the treatment of NSCLC.