Search

The simultaneous delivery of CpG oligonucleotide along with short interfering RNA (siRNA) has the potential to significantly boost the anticancer impact of siRNA medications. Our previous research demonstrated that Curdlan nanoparticles functionalized with adenosine are capable of selectively delivering therapeutic siRNA to cancerous cells through endocytosis mediated by adenosine receptors. Herein, we synthesized a dual-ligand-functionalized Curdlan polymer (denoted by CuMAN) to simultaneously target tumor cells and tumor-associated macrophages (TAMs). CuMAN nanoparticles containing CpG and siRNA demonstrated enhanced uptake by B16F10 tumor cells and bone marrow-derived macrophages, which are facilitated by AR on tumor cells and mannose receptor on macrophages. This led to increased release of pro-inflammatory cytokines in both in vitro and in vivo settings. The synergistic effect of CpG on TAMs and RNAi on tumor cells mediated by the CuMAN nanoparticle not only suppressed the tumor growth but also strongly inhibited the lung metastasis. Our findings indicate that the CuMAN nanoparticle has potential as an effective dual-targeting delivery system for nucleic acid therapeutics.

The Central Asian metallogenic domain (CAMD) is a multi-core metallogenic system controlled by boundary strike-slip fault systems. The Balkhash metallogenic belt in Kazakhstan, in which occur many large and super-large porphyritic Cu–Mo deposits and some quartz vein- and greisen-type W–Mo deposits, is a well-known porphyritic Cu–Mo metallogenic belt in the CAMD. In this paper 11 molybdenite samples from the western segment of the Balkhash metallogenic belt are selected for Re–Os compositional analyses and Re–Os isotopic dating. Molybdenites from the Borly porphyry Cu deposit and the three quartz vein-greisen W–Mo deposits—East Kounrad, Akshatau and Zhanet—all have relatively high Re contents (2712–2772 µg/g for Borly and 2.267–31.50 µg/g for the other three W–Mo deposits), and lower common Os contents (0.670–2.696 ng/g for Borly and 0.0051–0.056 ng/g for the other three). The molybdenites from the Borly porphyry Cu–Mo deposit and the East Kounrad, Zhanet, and Akshatau quartz vein- and greisen-type W–Mo deposits give average model Re–Os ages of 315.9 Ma, 298.0 Ma, 295.0 Ma, and 289.3 Ma respectively. Meanwhile, molybdenites from the East Kounrad, Zhanet, and Akshatau W–Mo deposits give a Re–Os isochron age of 297.9 Ma, with an MSWD value of 0.97. Re–Os dating of the molybdenites indicates that Cu–W–Mo metallogenesis in the western Balkhash metallogenic belt occurred during Late Carboniferous to Early Permian (315.9–289.3 Ma), while the porphyry Cu–Mo deposits formed at ~316 Ma, and the quartz vein-greisen W–Mo deposits formed at ~298 Ma. The Re–Os model and isochron ages thus suggest that Late Carboniferous porphyry granitoid and pegmatite magmatism took place during the late Hercynian movement. Compared to the Junggar-East Tianshan porphyry Cu metallogenic belt in northwestern China, the formation of the Cu–Mo metallogenesis in the Balkhash metallogenic belt occurred between that of the Tuwu-Yandong in East Tianshan and the Baogutu porphyry Cu deposits in West Junggar. Collectively, the large-scale Late Carboniferous porphyry Cu–Mo metallogenesis in the Central Asian metallogenic domain is related to Hercynian tectono-magmatic activities.

Review: 57 refs.