Division of Biophotonics and Imaging, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Biomedical Technology Wing, Trivandrum 695012, India.
Faraday Discuss. 2018 Apr 1;207:423-435. doi: 10.1039/c7fd00185a. Epub 2018 Jan 22.
Cancer, a condition with uncontrolled cell division, is the second leading cause of death worldwide. The currently available techniques for the imaging and treatment of cancer have their own limitations and hence a combination of more than one modality is expected to increase the efficacy of both diagnosis and treatment. In the present study, we have developed a multimodal imaging and therapeutic system by incorporating a chemotherapeutic drug, mitoxantrone (MTX) onto PEG coated gold nanorods (GNR). Strong absorption in the near-infrared (NIR) and visible regions qualifies GNR as an efficient photothermal (PTT) agent upon irradiation with either a NIR or visible laser. Additionally, the enhanced electric field of GNR makes it a suitable substrate for surface enhanced Raman scattering (SERS). Modification of GNR with amino PEG offers biocompatibility without affecting its optical property. In order to achieve tumor specificity, GNR-PEG was conjugated with tumor specific marker that can target cancer cells, leaving the normal cells unaffected. The incorporation of fluorescent chemotherapeutic drug mitoxantrone onto GNR-PEG facilitates chemotherapy as well as fluorescence imaging. The therapeutic efficacy of the developed GNR based system is tracked using fluorescence imaging and Raman imaging. The careful design of the system also facilitates the controlled release of the drug by photothermal triggering. Likewise, the imaging modality could be chosen as either Raman or fluorescence to monitor drug release in accordance with irradiation. The physico-chemical properties, and drug release profiles under different physiological conditions have been well studied. Finally, the developed system was tested for its therapeutic efficacy using cancer cells, in vitro. The receptor mediated cell uptake was more effective in folate receptor over-expressing cancer cells than in the normal and low-expressing cells. Accordingly the percentage of cell death was higher in folate receptor over-expressing cancer cells, which was further enhanced due to the effect of the dual therapeutic approach. The cell uptake and treatment efficacy was monitored using fluorescence microscopy and SERS. In conclusion, the developed GNR-PEG-MTX system is found to be an efficient multimodal therapeutic agent against cancer which could be tracked using two different techniques.
癌症是一种细胞失控分裂的疾病，是全球第二大致死原因。目前用于癌症成像和治疗的技术都有其自身的局限性，因此，多种模式的结合有望提高诊断和治疗的效果。在本研究中，我们通过将化疗药物米托蒽醌（MTX）结合到聚乙二醇（PEG）包覆的金纳米棒（GNR）上，开发了一种多模式成像和治疗系统。GNR 在近红外（NIR）和可见光区域具有很强的吸收能力，使其在近红外或可见激光照射下成为一种有效的光热（PTT）剂。此外，GNR 的增强电场使其成为表面增强拉曼散射（SERS）的合适基底。GNR 与氨基 PEG 的修饰在不影响其光学性能的情况下提供了生物相容性。为了实现肿瘤特异性，GNR-PEG 与肿瘤特异性标记物结合，能够靶向癌细胞，而不影响正常细胞。将荧光化疗药物米托蒽醌结合到 GNR-PEG 上，既可以进行化疗，又可以进行荧光成像。通过荧光成像和拉曼成像来跟踪所开发的基于 GNR 的系统的治疗效果。该系统的精心设计还便于通过光热触发控制药物的释放。同样，可以根据照射选择拉曼或荧光作为成像方式，以监测药物释放。已经很好地研究了该系统在不同生理条件下的物理化学性质和药物释放曲线。最后，在体外使用癌细胞对所开发的系统进行了治疗效果测试。在叶酸受体过表达的癌细胞中，受体介导的细胞摄取比在正常细胞和低表达细胞中更有效。因此，叶酸受体过表达的癌细胞的细胞死亡率更高，由于双重治疗方法的效果，进一步提高了细胞死亡率。使用荧光显微镜和 SERS 监测细胞摄取和治疗效果。总之，所开发的 GNR-PEG-MTX 系统被发现是一种有效的针对癌症的多模式治疗剂，可以使用两种不同的技术进行跟踪。
