Jia Ningyang, Zhang Shaojuan, Shao Pin, Bagia Christina, Janjic Jelena M, Ding Ying, Bai Mingfeng
Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University , Shanghai 200438, P. R. China.
Mol Pharm. 2014 Jun 2;11(6):1919-29. doi: 10.1021/mp5001923. Epub 2014 May 8.
The success of targeted cancer therapy largely relies upon the selection of target and the development of efficient therapeutic agents that specifically bind to the target. In the current study, we chose a cannabinoid CB2 receptor (CB2R) as a new target and used a CB2R-targeted photosensitizer, IR700DX-mbc94, for phototherapy treatment. IR700DX-mbc94 was prepared by conjugating a photosensitizer, IR700DX, to mbc94, whose binding specificity to CB2R has been previously demonstrated. We found that phototherapy treatment using IR700DX-mbc94 greatly inhibited the growth of CB2R positive tumors but not CB2R negative tumors. In addition, phototherapy treatment with nontargeted IR700DX did not show significant therapeutic effect. Similarly, treatment with IR700DX-mbc94 without light irradiation or light irradiation without the photosensitizer showed no tumor-inhibitory effect. Taken together, IR700DX-mbc94 is a promising phototherapy agent with high target-specificity. Moreover, CB2R appears to have great potential as a phototherapeutic target for cancer treatment.
靶向癌症治疗的成功很大程度上依赖于靶点的选择以及开发能特异性结合该靶点的高效治疗药物。在本研究中，我们选择大麻素CB2受体（CB2R）作为新靶点，并使用靶向CB2R的光敏剂IR700DX-mbc94进行光疗。IR700DX-mbc94是通过将光敏剂IR700DX与mbc94偶联制备而成，此前已证明mbc94对CB2R具有结合特异性。我们发现，使用IR700DX-mbc94进行光疗可显著抑制CB2R阳性肿瘤的生长，但对CB2R阴性肿瘤无效。此外，使用非靶向的IR700DX进行光疗未显示出显著的治疗效果。同样，在没有光照射的情况下使用IR700DX-mbc94治疗或在没有光敏剂的情况下进行光照射均未显示出肿瘤抑制作用。综上所述，IR700DX-mbc94是一种具有高靶向特异性的有前景的光疗药物。此外，CB2R作为癌症治疗的光疗靶点似乎具有巨大潜力。
