In Vivo Aggregation of Clearable Bimetallic Nanoparticles with Interlocked Surface Motifs for Cancer Therapeutics Amplification.

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.

Analysis of proto-type Tarim Basin in the late Precambrian and the dynamic mechanism of its evolution.

Tarim Basin has undergone an intricate tectonic evolution history ever since its formation from two discrete terranes in Neoproterozoic rather than in the Paleoproterozoic. More precisely, the amalgamation is assumed to happen during 1.0-0.8 Ga based on plate affinity. As the beginning of a unified Tarim block, studies of Tarim Basin in the Precambrian are basic and important. After the amalgamation of south and north paleo-Tarim terranes, Tarim block was experiencing a complicated tectonic process of being affected by mantle plume related to the breakup of Rodinia supercontinent in the south, and compressed by the Circum-Rodinia Subduction System in the north. The breakup of Rodinia supercontinent finished in the late Sinian Period, leading Kudi Ocean and Altyn Ocean to open and separating Tarim block from itself. According to the residual strata thickness, drilling data, and lithofacies distribution, the proto-type basin and tectono-paleogeographic maps of Tarim Basin in the late Nanhua Period and Sinian Period are reconstructed. With these maps, the characteristics of the rifts are revealed. Two rift systems were developed inside the unified Tarim Basin in the Nanhua Period and Sinian Period, one back-arc rift system in the northern margin and the other aulacogen system in the southern margin. The azimuth distribution of the rifts in Quruqtagh showed a predominant NE-SW trend, and the rifts in Aksu trended mainly NW-SE, while the rifts in Tiekelike trended SW-NE. With a three-dimensional elastic FEM (Finite Element Method) model that includes all rifts and deposited areas in Tarim Basin, applying the southern subduction and northern mantle upwelling properly to get the paleotectonic mian stress axes and the differential stress field, the dynamic mechanisms of rifts evolution are proved to be related to the peripheral tectonic environment mentioned above.

Rapid Biotransformation of Luminescent Bimetallic Nanoparticles in Hepatic Sinusoids.

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.