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Light-Controlled Generation of Singlet Oxygen within a Discrete Dual-Stage Metallacycle for Cancer Therapy
- Qin, Yi, Chen, Li-Jun, Dong, Fangyuan, Jiang, Shu-Ting, Yin, Guang-Qiang, Li, Xiaopeng, Tian, Yang, Yang, Hai-Bo
- Journal of the American Chemical Society 2019 v.141 no.22 pp. 8943-8950
- coordination compounds, cytotoxicity, endocytosis, energy transfer, in vivo studies, irradiation, nanoparticles, neoplasm cells, neoplasms, photochemotherapy, photosensitizing agents, singlet oxygen, water solubility
- Noninvasive control over the reversible generation of singlet oxygen (¹O₂) has found the practical significance in benefiting photodynamic therapy. In this study, we developed a new dual-stage metallacycle (M) by using a photosensitizer and photochromic switch as the functional building blocks, which enables the noninvasive “off–on” switching of ¹O₂ generation through the efficient intramolecular energy transfer. Due to the proximal placement of the functional entities within the well-defined metallacyclic scaffold, ¹O₂ generation in the ring-closed form state of the photochromic switch (C-M) is quenched by photoinduced energy transfer, whereas the generation of ¹O₂ in the ring-open form state (O-M) is activated upon light irradiation. More interestingly, the metallacycle-loaded nanoparticles with relatively high stability and water solubility were prepared, which allow for the delivery of metallacycles to cancer cells via endocytosis. Their theranostic potential has been systematically investigated both in vitro and in vivo. Under the light irradiation, the designed ring-open form nanoparticles (O-NPs) show remarkable higher cytotoxicity against cancer cells compared to the ring-closed form nanoparticles (C-NPs). In vivo experiments also revealed that tumors can be very efficiently eliminated by the designed nanoparticles under light irradiation with the ability to regulate in vivo generation of singlet oxygen. All these results demonstrated that the supramolecular coordination complexes with a dual-stage state provide a highly efficient nanoplatform for noninvasive control over the reversible generation of ¹O₂, thus allowing for their promising applications in tumor treatment and beyond.