Wang Xiaoqian, Hao Liying, Zhang Chaoliang, Chen Jiao, Zhang Ping
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, People's Republic of China.
J Biomater Appl. 2017 Mar;31(8):1108-1122. doi: 10.1177/0885328216689364. Epub 2017 Jan 13.
Targeted drug delivery is urgently needed for cancer therapy, and green synthesis is important for the biomedical use of drug delivery systems in the human body. In this work, we report two targeted delivery systems for anticancer drugs based on tea polyphenol functionalized and reduced graphene oxide (TPGs). The obtained TPGs demonstrated an efficient doxorubicin loading capacity as high as 3.430 × 10mg g and 3.932 × 10mg g, and exhibited pH-triggered release. Furthermore, the kinetic models, adsorption isotherms, and possible loading mechanisms were investigated in details. Compared to TPG1 and free doxorubicin, TPG2 is biocompatible to normal cells even at high concentrations and promotes tumor cells death by delivering the doxorubicin mainly to the nuclei. These results were confirmed using cell viability tests and confocal laser microscopy. Moreover, apoptosis tests showed that the mechanism of cancer cell death induced by TPG1 and TPG2 might follow the similar mechanisms. Taken together, these results demonstrate that TPGs provide a multifunctional drug delivery system with a greater loading capacity and pH-sensitive drug release for enhanced cancer therapy. The high drug payload capability and enhanced antitumor efficacy demonstrate that we developed systems are promising for various biomedical applications and cancer therapy.
癌症治疗迫切需要靶向给药，而绿色合成对于药物递送系统在人体中的生物医学应用至关重要。在这项工作中，我们报道了两种基于茶多酚功能化还原氧化石墨烯（TPGs）的抗癌药物靶向递送系统。所获得的TPGs表现出高效的阿霉素负载能力，高达3.430×10mg/g和3.932×10mg/g，并呈现pH触发释放。此外，还详细研究了动力学模型、吸附等温线和可能的负载机制。与TPG1和游离阿霉素相比，TPG2即使在高浓度下对正常细胞也具有生物相容性，并通过将阿霉素主要递送至细胞核来促进肿瘤细胞死亡。这些结果通过细胞活力测试和共聚焦激光显微镜得到证实。此外，凋亡测试表明，TPG1和TPG2诱导癌细胞死亡的机制可能遵循相似的机制。综上所述，这些结果表明TPGs提供了一种多功能药物递送系统，具有更大的负载能力和pH敏感的药物释放，可增强癌症治疗效果。高药物负载能力和增强的抗肿瘤疗效表明，我们开发的系统在各种生物医学应用和癌症治疗中具有广阔前景。
