Efficient antitumor effect of co-drug-loaded nanoparticles with gelatin hydrogel by local implantation.
Efficient antitumor effect of co-drug-loaded nanoparticles with gelatin hydrogel by local implantation.
复制标题
明胶水凝胶共载药纳米粒子局部植入的高效抗肿瘤作用
DOI：
10.1038/srep26546
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发表时间：
2016-05-26
影响因子：
4.6
通讯作者：
Sun W
中科院分区：
文献类型：
--
作者：
Zhang H;Tian Y;Zhu Z;Xu H;Li X;Zheng D;Sun W
粉防己碱（Tetrandrine, Tet）可以通过增加细胞内活性氧（Reactive Oxygen Species， ROS）水平来增强紫杉醇（Paclitaxel, Ptx）的抗肿瘤作用，从而可能导致两种药物共给药以协同抗肿瘤作用。在目前的研究中，我们报道了一种有效的局部治疗策略，利用纳米颗粒负载明胶系统有效地递送Tet和Ptx。将Tet-和Ptx共载的mPEG-PCL纳米颗粒（P/T-NPs）包封在物理交联的明胶水凝胶中，然后植入肿瘤部位，使药物持续释放。当温度缓慢升高时，载药明胶水凝胶发生相变。体外研究表明，包封在明胶水凝胶（P/T-NPs-明胶）内的负载Tet/ ptx的PEG-b-PCL纳米颗粒对BGC-823细胞的生长和侵袭能力的抑制作用比结合游离药物或P/T-NPs更有效。体内实验验证了P/ t - nps -明胶的治疗潜力。P/ t - nps -明胶显著抑制P - akt和下游抗凋亡Bcl-2蛋白的活化，并诱导促凋亡Bax蛋白的活化。此外，在NAC的影响下，P/ t - nps -明胶对相关蛋白的分子调节作用略有变化，这一点得到了肿瘤体积和重量观察的支持。基于这些发现，局部植入P/ t - nps -明胶可能是治疗胃癌的一种有前景的治疗策略。
Tetrandrine (Tet) could enhance the antitumor effect of Paclitaxel (Ptx) by increasing intracellular Reactive Oxygen Species (ROS) levels, which leads to the possibility of co-delivery of both drugs for synergistic antitumor effect. In the current study, we reported an efficient, local therapeutic strategy employing effective Tet and Ptx delivery with a nanoparticle-loaded gelatin system. Tet- and Ptx co-loaded mPEG-PCL nanoparticles (P/T-NPs) were encapsulated into the physically cross-linked gelatin hydrogel and then implanted on the tumor site for continuous drug release. The drug-loaded gelatin hydrogel underwent a phase change when the temperature slowly increased. In vitro study showed that Tet/Ptx-loaded PEG-b-PCL nanoparticles encapsulated within a gelatin hydrogel (P/T-NPs-Gelatin) inhibited the growth and invasive ability of BGC-823 cells more effectively than the combination of free drugs or P/T-NPs. In vivo study validated the therapeutic potential of P/T-NPs-Gelatin. P/T-NPs-Gelatin significantly inhibited the activation of p-Akt and the downstream anti-apoptotic Bcl-2 protein and also inducing the activation of pro-apoptotic Bax protein. Moreover, the molecular-modulating effect of P/T-NPs-Gelatin on related proteins varied slightly under the influence of NAC, which was supported by the observations of the tumor volumes and weights. Based on these findings, local implantation of P/T-NPs-Gelatin may be a promising therapeutic strategy for the treatment of gastric cancer.