The emergence of multiple drug delivery systems can solve the disadvantages of single-drug therapy, such as high dose and easy generation of drug resistance. Here, we designed a sialic acid–targeted dextran-mercaptopurine prodrug linked by carbonyl vinyl sulfide for coordinate ZnO quantum dots to achieve multiple drug delivery (doxorubicin, 5-fluorouracil, 6-mercaptopurine), which can be released under the trigger of pH and glutathione. To enhance the antitumor effect, we used inorganic photosensitizer CdSe quantum dots to achieve photodynamic therapy, which can produce cytotoxic reactive oxygen species (hydroxyl radicals) under light conditions. Notably, we found that glutathione is consumed by the delivery of 6-mercaptopurine. It is able to efficiently amplify intracellular oxidative stress via increasing •OH generation. After chelating 99mTc4+ radioisotopes by diethylenetriamine pentaacetic acid, the drug delivery system could be tracked under in vivo single-photon emission computed tomography imaging. The results showed that the phenylboronic acid targeting substance can specifically recognize sialic acid, so that the drug system has a good accumulation in the tumor site, which can better increase the therapeutic effect. Compared to free doxorubicin, the drug system can reduce the IC50 value of cells 4.4-fold under light conditions and significantly inhibit tumor growth in vivo. These data indicate that the sialic acid–targeted nanomedicine system has achieved ideal antitumor effects and apparent photodynamic therapy effects and has broad application prospects.

中文翻译：

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用于 pH 和谷胱甘肽触发的多重抗癌药物释放和增强氧化应激的唾液酸靶向药物递送和成像系统

多种给药系统的出现，可以解决单药治疗剂量大、易产生耐药性等弊端。在这里，我们设计了一种唾液酸靶向的葡聚糖-巯基嘌呤前药，由羰基乙烯基硫化物连接，用于配位 ZnO 量子点以实现多种药物递送（多柔比星、5-氟尿嘧啶、6-巯基嘌呤），可在 pH 和谷胱甘肽。为了增强抗肿瘤作用，我们使用无机光敏剂 CdSe 量子点来实现光动力疗法，它可以在光照条件下产生细胞毒性活性氧（羟基自由基）。值得注意的是，我们发现谷胱甘肽被 6-巯基嘌呤的递送所消耗。它能够通过增加•OH 的生成来有效地放大细胞内氧化应激。通过二亚乙基三胺五乙酸螯合 99mTc4+ 放射性同位素后，可以在体内单光子发射计算机断层扫描成像下跟踪药物递送系统。结果表明，苯基硼酸靶向物质可以特异性识别唾液酸，使药物系统在肿瘤部位有良好的积累，可以更好地提高治疗效果。与游离多柔比星相比，该药物系统在光照条件下可将细胞的IC50值降低4.4倍，并在体内显着抑制肿瘤生长。这些数据表明，唾液酸靶向纳米药物系统取得了理想的抗肿瘤效果和明显的光动力治疗效果，具有广阔的应用前景。可以在体内单光子发射计算机断层扫描成像下跟踪药物输送系统。结果表明，苯基硼酸靶向物质可以特异性识别唾液酸，使药物系统在肿瘤部位有良好的积累，可以更好地提高治疗效果。与游离多柔比星相比，该药物系统在光照条件下可将细胞的IC50值降低4.4倍，并在体内显着抑制肿瘤生长。这些数据表明，唾液酸靶向纳米药物系统取得了理想的抗肿瘤效果和明显的光动力治疗效果，具有广阔的应用前景。可以在体内单光子发射计算机断层扫描成像下跟踪药物输送系统。结果表明，苯基硼酸靶向物质可以特异性识别唾液酸，使药物系统在肿瘤部位有良好的积累，可以更好地提高治疗效果。与游离多柔比星相比，该药物系统在光照条件下可将细胞的IC50值降低4.4倍，并在体内显着抑制肿瘤生长。这些数据表明，唾液酸靶向纳米药物系统取得了理想的抗肿瘤效果和明显的光动力治疗效果，具有广阔的应用前景。使药物系统在肿瘤部位有良好的积累，可以更好的增加治疗效果。与游离多柔比星相比，该药物系统在光照条件下可将细胞的IC50值降低4.4倍，并在体内显着抑制肿瘤生长。这些数据表明，唾液酸靶向纳米药物系统取得了理想的抗肿瘤效果和明显的光动力治疗效果，具有广阔的应用前景。使药物系统在肿瘤部位有良好的积累，可以更好的增加治疗效果。与游离多柔比星相比，该药物系统在光照条件下可将细胞的IC50值降低4.4倍，并在体内显着抑制肿瘤生长。这些数据表明，唾液酸靶向纳米药物系统取得了理想的抗肿瘤效果和明显的光动力治疗效果，具有广阔的应用前景。