Abstract:
This study focuses on the design and evaluation of redox-responsive nanoparticles (NPs) by synthesizing disulfide-containing N-phthaloyl chitosan-SS-methoxy poly(ethylene glycol) (NPC-SS-mPEG) and incorporating the anti-cancer drug doxorubicin into the NPs. The structural features of NPC-SS-mPEG were investigated using FTIR, NMR, XRD, and TGA/DTA analysis. DLS and TEM analysis confirmed the particle size and morphology of the NPs. The stability of the NPs was measured with the presence and absence of glutathione (GSH) in buffers pH 5 and 7.4. Furthermore, the release of DOX from the NPs was studied in GSH (10 mM) containing/absent medium at pH 5 and pH 7.4 which mimics the intracellular environment with redox potential. The results indicated a significantly increased release of DOX in the GSH containing medium pH 5 (82.9 ± 2.1 %) and pH 7.4 (67.37 ± 0.88 %) compared to the GSH free pH 7.4 (29.99 ± 1.01 %) and pH 5 medium (56.56 ± 1.7 %) at 60 h. The cytotoxicity study in the MDA-MB-231 breast cancer cell line by MTT assay indicated higher toxicity of redox-responsive NPs to cancer cells than free DOX. In concurrence with the cytotoxicity assay, in-vitro fluorescence staining assays (AO/EB, Hoechst, ROS generation) also confirmed that NPs loaded with DOX induce higher toxicity to cancer cells than free DOX. Taken together, the overall results confirmed the superiority of the redox response-mediated release of DOX in effectively controlling cancer progression.
摘要:
这项研究的重点是通过合成含二硫化物的N-邻苯二酰基壳聚糖-SS-甲氧基聚(乙二醇)(NPC-SS-mPEG)并将抗癌药物多柔比星掺入到纳米粒子中,设计和评估氧化还原响应纳米粒子(NPs)。利用FTIR研究了NPC-SS-mPEG的结构特征,NMR,XRD,和TGA/DTA分析。DLS和TEM分析证实了NP的粒度和形态。在缓冲液pH5和7.4中存在和不存在谷胱甘肽(GSH)的情况下测量NP的稳定性。此外,在pH5和pH7.4的含/不含GSH(10mM)的培养基中研究了DOX从NP的释放,该培养基模拟了具有氧化还原电位的细胞内环境。结果表明,与不含GSH的pH7.4(29.99±1.01%)和pH5的培养基(56.56±1.7%)相比,含GSH的pH5(82.9±2.1%)和pH7.4(67.37±0.88%)的培养基中DOX的释放显着增加60小时。通过MTT测定在MDA-MB-231乳腺癌细胞系中进行的细胞毒性研究表明,无氧化还原反应NP对DOX的毒性更高与细胞毒性测定同时进行,体外荧光染色测定(AO/EB,Hoechst,ROS的产生)也证实了负载有DOX的NP比游离DOX对癌细胞诱导更高的毒性。一起来看,总体结果证实了氧化还原反应介导的DOX释放在有效控制癌症进展方面的优越性.