Li Youyou, Han Wenbo, Gong Deyan, Luo Taokun, Fan Yingjie, Mao Jianming, Qin Wenwu, Lin Wenbin
Department of Chemistry, The University of Chicago Chicago Illinois 60637 USA
Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province and State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University Lanzhou 730000 China.
Chem Sci. 2023 Apr 19;14(19):5106-5115. doi: 10.1039/d3sc00455d. eCollection 2023 May 17.
We report the self-assembly of amphiphilic BDQ photosensitizers into lysosome-targeting nanophotosensitizer BDQ-NP for highly effective photodynamic therapy (PDT). Molecular dynamics simulation, live cell imaging, and subcellular colocalization studies showed that BDQ strongly incorporated into lysosome lipid bilayers to cause continuous lysosomal membrane permeabilization. Upon light irradiation, the BDQ-NP generated a high level of reactive oxygen species to disrupt lysosomal and mitochondrial functions, leading to exceptionally high cytotoxicity. The intravenously injected BDQ-NP accumulated in tumours to achieve excellent PDT efficacy on subcutaneous colorectal and orthotopic breast tumor models without causing systemic toxicity. BDQ-NP-mediated PDT also prevented metastasis of breast tumors to the lungs. This work shows that self-assembled nanoparticles from amphiphilic and organelle-specific photosensitizers provide an excellent strategy to enhance PDT.
我们报道了两亲性BDQ光敏剂自组装成靶向溶酶体的纳米光敏剂BDQ-NP，用于高效光动力疗法（PDT）。分子动力学模拟、活细胞成像和亚细胞共定位研究表明，BDQ强烈掺入溶酶体脂质双层，导致溶酶体膜持续通透化。光照后，BDQ-NP产生高水平的活性氧，破坏溶酶体和线粒体功能，导致极高的细胞毒性。静脉注射的BDQ-NP在肿瘤中蓄积，在皮下结直肠癌和原位乳腺癌模型上实现了优异的PDT疗效，且未引起全身毒性。BDQ-NP介导的PDT还可预防乳腺癌转移至肺部。这项工作表明，由两亲性和细胞器特异性光敏剂自组装而成的纳米颗粒为增强PDT提供了一种优异的策略。
