MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.
MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.
Biomaterials. 2014 Apr;35(13):4185-94. doi: 10.1016/j.biomaterials.2014.01.044. Epub 2014 Feb 7.
A number of anticancer drugs, such as doxorubicin (DOX), operate only after being transported into the nucleus of cancer cells. Thus it is essential for the drug carriers to effectively release the anticancer drugs into the cytoplasm of cancer cells and make them move to nucleus freely. Herein, a pH-responsive charge-reversal polyelectrolyte and integrin αⅤβ3 mono-antibody functionalized graphene oxide (GO) complex is constituted as a nanocarrier for targeted delivery and controlled release of DOX into cancer cells. The DOX loading and releasing in vitro demonstrates that this nanocarrier cannot only load DOX with high efficiency, but also effectively release it under mild acidic pH stimulation. Cellular toxicity assay, confocal laser scanning microscopy and flow cytometer analysis results together confirm that with the targeting nanocarrier, DOX can be selectively transported into the targeted cancer cells. Then they will be effectively released from the nanocarriers in cytoplasm and moved into the nucleus subsequently, stimulating by charge-reverse of the polyelectrolyte in acidic intracellular compartments. The effective delivery and release of the anticancer drugs into nucleus of the targeted cancer cells will lead to a high therapeutic efficiency. Hence, such a targeting nanocarrier prepared from GO and charge-reversal polyelectrolytes is likely to be an available candidate for targeted drug delivery in tumor therapy.
许多抗癌药物,如阿霉素(DOX),只有在被运输到癌细胞的核内后才会起作用。因此,对于药物载体来说,将抗癌药物有效地释放到癌细胞的细胞质中,并使它们自由移动到细胞核中是至关重要的。在此,我们构建了一种 pH 响应的电荷反转聚电解质和整合素 αⅤβ3 单抗体功能化的氧化石墨烯(GO)复合物作为纳米载体,用于 DOX 向癌细胞的靶向传递和控制释放。体外 DOX 的负载和释放实验表明,这种纳米载体不仅可以高效地负载 DOX,而且可以在温和的酸性 pH 刺激下有效地释放 DOX。细胞毒性试验、共聚焦激光扫描显微镜和流式细胞仪分析结果共同证实,通过靶向纳米载体,DOX 可以选择性地运输到靶向癌细胞。然后,在细胞质中从纳米载体中有效释放,并随后进入细胞核,这是由酸性细胞内隔室中聚电解质的电荷反转所刺激的。抗癌药物有效递送到靶向癌细胞的细胞核中,将导致高治疗效率。因此,由 GO 和电荷反转聚电解质制备的这种靶向纳米载体可能是肿瘤治疗中靶向药物递送的一种可行候选物。
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