A major goal in cancer research is to develop carriers that can deliver drugs effectively and without side effects. Liposomal and particulate carriers with diameters of ∼100 nm have been widely used to improve the distribution and tumour accumulation of cancer drugs, but so far they have only been effective for treating highly permeable tumours. Here, we compare the accumulation and effectiveness of different sizes of long-circulating, drug-loaded polymeric micelles (with diameters of 30, 50, 70 and 100 nm) in both highly and poorly permeable tumours. All the polymer micelles penetrated highly permeable tumours in mice, but only the 30 nm micelles could penetrate poorly permeable pancreatic tumours to achieve an antitumour effect. We also showed that the penetration and efficacy of the larger micelles could be enhanced by using a transforming growth factor-β inhibitor to increase the permeability of the tumours.
Nicotianamine (NA), a chelator of metals, is ubiquitously present in higher plants. Nicotianamine aminotransferase (NAAT) catalyzes the amino group transfer of NA in the biosynthetic pathway of phytosiderophores and is essential for iron acquisition in graminaceous plants. The gene that encodes NAAT from barley was introduced into the nongraminaceous plant tobacco, which produces NA but not phytosiderophores. Transgenic tobacco plants (naat tobacco) that constitutively expressed the NAAT gene had young leaves with interveinal chlorosis and flowers that were abnormally shaped and sterile. Endogenous NA was consumed as a result of NAAT overproduction in naat tobacco. The resulting NA shortage caused disorders in internal metal transport, leading to these abnormal phenotypes. In addition to its role in long-distance metal transport, NA may be involved in the regulation of metal transfer within the cells. These results suggest that a shortage of NA impaired the functions of metal-requiring proteins, including transcription factors.
Engineered nanoparticles that respond to pathophysiological parameters, such as pH or redox potential, have been developed as contrast agents for the magnetic resonance imaging (MRI) of tumours. However, beyond anatomic assessment, contrast agents that can sense these pathological parameters and rapidly amplify their magnetic resonance signals are desirable because they could potentially be used to monitor the biological processes of tumours and improve cancer diagnosis. Here, we report an MRI contrast agent that rapidly amplifies magnetic resonance signals in response to pH. We confined Mn(2+) within pH-sensitive calcium phosphate (CaP) nanoparticles comprising a poly(ethylene glycol) shell. At a low pH, such as in solid tumours, the CaP disintegrates and releases Mn(2+) ions. Binding to proteins increases the relaxivity of Mn(2+) and enhances the contrast. We show that these nanoparticles could rapidly and selectively brighten solid tumours, identify hypoxic regions within the tumour mass and detect invisible millimetre-sized metastatic tumours in the liver.
Nb 2 O 5 exhibits various crystal systems, such as orthorhombic ͑o͒, tetragonal ͑t͒, and monoclinic ͑m͒, among which Nb 2 O 5 synthesized at 900-1000°C is commercially used as a cathode material of the 2-V lithium ion battery. The battery performances depended on the structure of Nb 2 O 5 , and the t-Nb 2 O 5 synthesized at 1000°C exhibited an excellent cycling performance with a large discharge capacity of 190 mAh ͑g oxide͒ −1 . The structural variations of Nb 2 O 5 during electrochemical reaction were examined. The in situ synchrotron radiation-X-ray diffraction ͑XRD͒ measurement indicated that o-and t-Nb 2 O 5 maintain their original crystal lattices, accompanying a small change in the cell volume even after the Li intercalation. The in situ X-ray absorption fine structure ͑XAFS͒ analysis of o-and t-Nb 2 O 5 revealed that the continuous variation from Nb 5+ to Nb 4+ took place during the intercalation process. A significant rearrangement of the Nb-O octahedra accompanied by the change of Nb-O and Nb-Nb interactions occurred in both structures with Li intercalation. XRD and XAFS data suggests that the two-dimensional layer structure of t-Nb 2 O 5 seems to be more flexible regarding the Li intercalation compared with the three-dimensional structure of o-Nb 2 O 5 . This may account for the better cyclic performance of the former material as the electrode material.
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