Abstract
Photodynamic therapy (PDT) is a precise and less toxic side effect treatment strategy. However, the inherently short lifespan and constrained diffusion range of reactive oxygen species within the cellular milieu can attenuate the therapeutic efficacy of cytoplasmic photosensitizers. Organelle-targeted PDT is thus proposed. Although the essence of PDT is the photosensitization reaction accompanied by biological effects involving aerobic molecules, mitochondria-targeted PDT may lead to the emergence of drug resistance in tumor cells triggered by mitochondrial damage. Thus, developing more types of organelle-targeted PDT strategies is the key to avoiding this problem. Herein, a fluoroboron dipyrrole-based photosensitizer, OFBDP, with Golgi apparatus-targeted and PDT ability is designed and synthesized. Furthermore, considering the effect of high concentrations of reduced glutathione in tumor cells, the addition of glutaminase inhibitor, compound 968 (C968), synergistically enhanced the PDT efficacy of OFBDP by indirectly inhibiting intracellular glutathione synthesis through its effect on glutamine metabolism. The OFBDP/C968 combination has demonstrated an enhanced tumor ablation capability. This work generally provides a strategy for the potential of organelle-targeted PDT to improve treatment outcomes, but also contribute to the burgeoning field of subcellular photosensitizer research.
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