Liver sequestration, mainly resulting from the phagocytosis of mononuclear phagocyte system (MPS) cells, is a long-standing barrier in nanoparticle delivery, which severely decreases the disease-targeting ability, leads to nanotoxicity, and inhibits clinical translation. To avoid long-term liver sequestration, we elaborately designed luminescent gold–silver bimetallic nanoparticles that could be rapidly transformed by the hepatic sinusoidal microenvironment rich in glutathione and oxygen, significantly different from monometallic gold nanoparticles that were rapidly sequestrated by Kupffer cells due to the much slower biotransformation. We found that the rapid sinusoidal biotransformation induced by the synergistic reactions of glutathione and oxygen with the reactive silver atoms could help bimetallic nanoparticles to avoid MPS phagocytosis, promote fast release from the liver, prolong blood circulation, enhance renal clearance, and increase disease targeting. With the fast biotransformation in sinusoids, liver sequestration could be turned into a beneficial storage mechanism for nanomedicines to maximize targeting.

No abstract

Although renal-clearable luminescent metal nanoparticles (NPs) have been widely developed, their application to efficient cancer therapy is still limited due to low reactive oxygen species (ROS) production. Here, a novel system of clearable mercaptosuccinic acid (MSA) coated Au−Ag bimetallic NPs is designed to enhance ROS production. The results show that the strong COO−Ag coordination bonds between the carboxylic acid groups of MSA and Ag atoms on the Au−Ag bimetallic NPs could construct high-rigidity interlocked surface motifs to restrict the intrananoparticle motions for enhanced ROS generation. Moreover, bimetallic NPs exhibit pH-responsive self-assembly capability under the acidic environment inside lysosomes of cancer cells at both in vitro and in vivo, restricting the internanoparticle motions to further boost ROS production. The well-designed bimetallic NPs show high tumor targeting efficiency, fast elimination from the body through rapid liver biotransformation, and extensive destruction to cancer cells, resulting in good security and prominent therapeutic performance.

Tarim Basin is a large, superimposed basin rich in petroleum resources, which has experienced many stages of complex tectonic-sedimentary evolution. As the basic geological study of the Tarim Basin, the proto-type basin and tectono-paleogeographic evolution are of great significance for understanding the distribution of petroleum reservoirs in the superimposed basin and provide tectonic background and theoretical guidance for petroleum exploration. According to the residual thickness map, as well as other lithofacies and seismic data, the scopes of the proto-type basin are determined by the marginal facies method and the thickness trend method, and the shortening amounts are calculated by the balanced cross-section method. Based on these data and previous works, four proto-type basin maps of Tarim Basin in present-day geographic coordinates and four tectono-paleogeographic maps of Tarim Basin in paleogeographic coordinates during the early Paleozoic are reconstructed, which directly show the changes of sedimentary and uplift-depression pattern caused by the transformation of the tectonic environment from extension to compression. In the Cambrian, the Tarim Basin was controlled by the extensional tectonic environment, with the sedimentary framework of “carbonate platform in the west, deep-water basin in the east”. At the end of the Ordovician, the Kudi Ocean and the North Altyn Ocean were closed, and the Central and South Kunlun terrane and the Altyn-Qilian terrane were collaged with the Tarim block, which directly led to the transformation of the uplift-depression pattern in the Tarim Basin from east-west differentiation to north-south differentiation, thus changing the sedimentary environment of the Tarim Basin in the late Ordovician to Silurian.

The Tarim basin is a large composite and superimposed sedimentary basin that has undergone complex multi-period and polycyclic tectonic movements. Understanding the proto-type basin and tectono-paleogeographic evolution of this complex superimposed basin is important for understanding the basin-mountain coupling and dynamical mechanisms of the Paleo-Asian and Tethys tectonic systems as well as hydrocarbon exploration and development. Based on previous works, together with the recent exploration, and geological evidences, three global plate tectonic pattern maps, four Tarim proto-type basin maps (in present-day geographic coordinates) and four regional tectono-paleogeography maps (in paleogeographic coordinates) during the Late Paleozoic are provided in this paper. Based on these maps, the proto-type basin and tectono-paleogeographic features of the Tarim basin during the Late Paleozoic are illustrated. The Devonian to Permian is an important period of terranes/island-arcs accretion and oceanic closure along the periphery of the Tarim block, and a critical period when the polarity of Tarim basin (orientation of basin long-axis) rotated at the maximum angle clockwise. During the Late Paleozoic, the periphery of the Tarim block was first collisional orogeny on its northern margin, followed by continuous collisional accretion of island arcs on its southern margin: on the Northern margin, the North and South Tianshan Oceans closed from East to West; on the South-Western margin, the Tianshuihai Island Arc gradually collided and accreted. These tectonic events reduced the extent of the seawater channel of the passive continental margin in the Western part of the basin until its complete closure at the end of the Permian. The Tarim basin was thus completely transformed into an inland basin. This is a process of regression and uplift. The Southwest of the Tarim basin changed from a passive to an active continental margin, through back-arc downwarping and eventually complete closure to foreland setting. The intra-basin lithofacies range from shelf-littoral to platform-tidal flat to alluvial plain-lacustrine facies. The tectonic-sedimentary evolution of the Tarim basin is strongly controlled by peripheral geotectonic setting.