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首页> 外文期刊>Materials science & engineering >Effect of drug precursor in cell uptake and cytotoxicity of redox-responsive camptothecin nanomedicines
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Effect of drug precursor in cell uptake and cytotoxicity of redox-responsive camptothecin nanomedicines

机译：药物前体对氧化还原反应性喜树碱纳米药物的细胞摄取和细胞毒性的影响

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摘要

Novel redox-responsive nanomedicines have been synthesized by conjugating camptothecin prodrugs ((pyri-dine-2-yldisulfanil)alkyl carbonate derivatives) to hybrid porous silica nanoparticles through disulfide bond. After disulfide reduction, camptothecin may be released by an intramolecular cyclization mechanism or by carbonate bond hydrolysis. Samples have been characterized by physico-chemical techniques, and stability and drug release in PBS and human serum have been determined. Moreover, cell uptake was studied by fluorescence microscopy and flow cytometry, whilst cytotoxic activity was validated by MTT test Obtained results indicate that prodrug side chain carbon number (n = 1,23) determines material hydrophobic properties and, as a consequence, its stability in aqueous medium. When n value increases, the negative surface charge decreases dramatically due to a shielding effect provoked by hydrophobic ligands, which promotes particle aggregation and favors cell internalization. Furthermore, the n value determines the type of products released and, subsequently, the cytotoxic activity. Full disulfide bridge reduction takes place in all cases, but quick delivery of the free drug by intramolecular cyclization is only possible with the shortest linker (n = 1), whereas other nanomedicines only present slow discharge of camptothecin by carbonate hydrolysis. Overall, the drug precursor incorporated to the inorganic nanoplatform modulates both cell uptake rate and cytotoxicity according to the different functional ization.
机译：通过将喜树碱前药（碳酸（吡啶并二-2-基二硫基）烷基酯衍生物）与二氧化硫键杂化成多孔二氧化硅纳米粒子，可以合成出新型的氧化还原反应性纳米药物。二硫化物还原后，喜树碱可通过分子内环化机理或通过碳酸酯键水解而释放。样品已通过理化技术进行了表征，并且已经确定了在PBS和人血清中的稳定性和药物释放。此外，通过荧光显微镜和流式细胞术研究了细胞摄取，同时通过MTT测试验证了细胞毒性活性。获得的结果表明，前药侧链碳原子数（n = 1,23）决定了材料的疏水性，并因此决定了其稳定性。水性介质。当n值增加时，由于疏水配体引起的屏蔽作用，负表面电荷急剧下降，这促进了颗粒聚集并有利于细胞内化。此外，n值决定了释放产物的类型，进而决定了细胞毒活性。在所有情况下均会发生二硫键的完全还原，但是只有通过最短的连接子（n = 1）才能通过分子内环化快速释放游离药物，而其他纳米药物只能通过碳酸盐水解缓慢释放喜树碱。总体而言，结合到无机纳米平台中的药物前体根据不同的功能化作用来调节细胞摄取率和细胞毒性。

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