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ATIQCTPC: a nanomedicine capable of targeting tumor and blocking thrombosis in vivo

机译：ATIQCTPC：一种能够在体内靶向肿瘤并阻断血栓形成的纳米药物

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To overcome the harmful side effects, low tolerance, and undesirable outcomes of the anticancer drugs, we used ethane-1,2-diamine to bridge antitumoral ( S )-3-acetyl-4-oxo-tetrahydroindolo[2,3-a]quinolizine-6-carboxylic acid (ATIQC) and tumor-targeting d-glucuronic acid, thereby providing (6 S )-3-acetyl-4-oxo- N -(2-(3,4,5,6-tetrahydroxytetrahydro-2H-pyran-2-carboxamido)ethyl)-4,6,7,12-tetrahydroindolo[2,3-a]quinolizine-6-carboxamide (ATIQCTPC). Atomic force microscopy images visualized, that in serum, ATIQCTPC formed particles of height <81?nm. These particles effectively avoided phagocytosis of macrophages and were stable in blood circulation. Distribution analysis indicated that ATIQCTPC accumulated and released ATIQC in the tumor tissue through a targeting manner. Thus, the antitumor and the anti-thrombotic activities of ATIQCTPC were 100-fold higher than those of ATIQC, and ATIQCTPC was able to prevent cancer patients from suffering from thrombosis. Based on the observation that ATIQCTPC decreased serum tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) in S180 mice, we hypothesized that this is the mechanism that ATIQCTPC utilized to slow tumor growth. Additionally, we observed that ATIQCTPC inhibited thrombosis by decreasing serum P-selectin of thrombotic rats. The intermolecular association and the hexamerization manner of ATIQCTPC were experimentally evidenced and correlated with the formation of the nanoparticles.
机译：为克服抗癌药的有害副作用，耐受性差和不良结果，我们使用乙烷-1,2-二胺桥接抗肿瘤的（S）-3-乙酰基-4-氧代四氢吲哚[2,3-a]喹啉6羧酸（ATIQC）和靶向肿瘤的d-葡萄糖醛酸，从而提供（6 S）-3-乙酰-4-氧代-N-（2-（3,4,5,6-四羟基四氢-2H -吡喃-2-甲酰胺基）-4,6,7,12-四氢吲哚并[2,3-a]喹啉嗪-6-羧酰胺（ATIQCTPC）。可见的原子力显微镜图像显示，ATIQCTPC在血清中形成了高度<81？nm的颗粒。这些颗粒有效地避免了巨噬细胞的吞噬作用，并且在血液循环中稳定。分布分析表明，ATIQCTPC通过靶向方式在肿瘤组织中积累和释放。因此，ATIQCTPC的抗肿瘤和抗血栓形成活性比ATIQC高100倍，并且ATIQCTPC能够预防癌症患者遭受血栓形成。基于观察到ATIQCTPC降低了S180小鼠的血清肿瘤坏死因子-α（TNF-α）和白细胞介素8（IL-8），我们推测这是ATIQCTPC用于减缓肿瘤生长的机制。此外，我们观察到ATIQCTPC通过降低血栓形成大鼠的血清P-选择素抑制血栓形成。实验证明了ATIQCTPC的分子间缔合和六聚化方式，并与纳米粒子的形成相关。

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