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Abstract：
Chemotherapy fails to achieve an ideal gliomas therapy due to the limited delivery of chemotherapeutics across the blood brain barrier (BBB), difficult accumulation of drugs in the gliomas area, and off-target toxicity. Herein, the pH-triggered small molecule nano-prodrugs (Try-CA-NPs) emulsified from hydrophobic tryptamine (Try)-cinnamaldehyde (CA) twin drug were successfully prepared through a facile method. Try-CA-NPs exhibited long-term storage and circulation stability. Furthermore, liposoluble Try-CA-NPs could easily cross BBB and efficiently accumulate in brain, selectively target to gliomas cells via Try-mediated cellular uptake, and enhance cytotoxicity through intracellular pH-triggered endosomal escape and efficient drug release, and synergistic effect between CA and Try, therefore achieving the complete destruction of SH-SY5Y multicellular spheroids (MCs). Thus, the pH-triggered small molecule nano-prodrugs emulsified from Try-CA twin drug have the great potential for clinically targeted synergistic glioma therapy.
摘要：
由于化疗药物通过血脑屏障（BBB）的递送有限，化疗无法获得理想的神经胶质瘤治疗。难以在神经胶质瘤区域积累药物，和脱靶毒性。在这里，通过简便的方法成功地制备了由疏水性色胺（Try）-肉桂醛（CA）双药乳化的pH触发的小分子纳米前药（Try-CA-NPs）。Try-CA-NP表现出长期储存和循环稳定性。此外，脂溶性Try-CA-NP可以轻松穿过BBB并在大脑中有效积累，通过Try介导的细胞摄取选择性靶向胶质瘤细胞，并通过细胞内pH触发的内体逃逸和有效的药物释放来增强细胞毒性，CA和Try之间的协同作用，因此实现SH-SY5Y多细胞球体（MC）的完全破坏。因此，由Try-CA双生子药物乳化的pH触发的小分子纳米前药在临床靶向协同治疗胶质瘤方面具有巨大潜力。
