Ye Shuyue, Rao Jiaming, Qiu Shihong, Zhao Jinglong, He Hui, Yan Ziling, Yang Tao, Deng Yibin, Ke Hengte, Yang Hong, Zhao Yuliang, Guo Zhengqing, Chen Huabing
State Key Laboratory of Radiation Medicine and Protection, Jiangsu Key Laboratory of Neuropsychiatric Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and School of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, China.
Adv Mater. 2018 Jun 3:e1801216. doi: 10.1002/adma.201801216.
High-performance photosensitizers are highly desired for achieving selective tumor photoablation in the field of precise cancer therapy. However, photosensitizers frequently suffer from limited tumor suppression or unavoidable tumor regrowth due to the presence of residual tumor cells surviving in phototherapy. A major challenge still remains in exploring an efficient approach to promote dramatic photoconversions of photosensitizers for maximizing the anticancer efficiency. Here, a rational design of boron dipyrromethene (BDP)-based conjugated photosensitizers (CPs) that can induce dually cooperative phototherapy upon light exposure is demonstrated. The conjugated coupling of BDP monomers into dimeric BDP (di-BDP) or trimeric BDP (tri-BDP) induces photoconversions from fluorescence to singlet-to-triplet or nonradiative transitions, together with distinctly redshifted absorption into the near-infrared region. In particular, tri-BDP within nanoparticles shows preferable conversions into both primary thermal effect and minor singlet oxygen upon near-infrared light exposure, dramatically achieving tumor photoablation without any regrowth through their cooperative anticancer efficiency caused by their dominant late apoptosis and moderate early apoptosis. This rational design of CPs can serve as a valuable paradigm for cooperative cancer phototherapy in precision medicine.
在精准癌症治疗领域，实现选择性肿瘤光消融非常需要高性能的光敏剂。然而，由于光疗中存在存活的残余肿瘤细胞，光敏剂经常受到肿瘤抑制有限或不可避免的肿瘤复发的困扰。在探索一种有效的方法以促进光敏剂的显著光转化以最大化抗癌效率方面，仍然存在重大挑战。在此，展示了一种基于硼二吡咯亚甲基（BDP）的共轭光敏剂（CPs）的合理设计，该光敏剂在光照下可诱导双重协同光疗。BDP单体共轭偶联成二聚体BDP（di-BDP）或三聚体BDP（tri-BDP）会诱导从荧光到单重态到三重态或非辐射跃迁的光转化，同时吸收明显红移至近红外区域。特别地，纳米颗粒中的tri-BDP在近红外光照射下表现出向主要热效应和少量单线态氧的优选转化，通过其由主要晚期凋亡和中度早期凋亡引起的协同抗癌效率，显著实现肿瘤光消融且无任何复发。这种CPs的合理设计可作为精准医学中协同癌症光疗的有价值范例。
