Liang Xiaolong, Chen Min, Bhattarai Pravin, Hameed Sadaf, Dai Zhifei
Department of Ultrasound, Peking University Third Hospital, Beijing 100191, China.
Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.
ACS Nano. 2020 Oct 27;14(10):13569-13583. doi: 10.1021/acsnano.0c05617. Epub 2020 Sep 16.
Photodynamic therapy (PDT) shows great promise for the treatment of colon cancer. However, practically, it is a great challenge to use a nanocarrier for the codelivery of both the photosensitizer and oxygen to improve PDT against PDT-induced hypoxia, which is closely related to tumor metastasis. Hence, an effective strategy was proposed to develop an oxygen self-supplemented PDT nanocarrier based on the ultrasonic dispersion of perfluorooctyl bromide (PFOB) liquid into the preformed porphyrin grafted lipid (PGL) nanoparticles (NPs) with high porphyrin loading content of 38.5%, followed by entrapping oxygen. Interestingly, the orderly arranging mode of porphyrins and alkyl chains in PGL NPs not only guarantees a high efficacy of singlet oxygen generation but also reduces fluorescence loss of porphyrins to enable PGL NPs to be highly fluorescent. More importantly, PFOB liquid was stabilized inside PGL NPs with an ultrahigh loading content of 98.15% due to the strong hydrophobic interaction between PGL and PFOB molecules, facilitating efficient oxygen delivery. Both and results demonstrated that the obtained O@PFOB@PGL NPs could act as a prominent oxygen reservoir and effectively replenish oxygen into the hypoxic tumors with no need for external stimulation, conducive to augmented singlet oxygen generation, hypoxia relief, and subsequent downregulation of COX-2 expression. As a result, the use of O@PFOB@PGL NPs for hypoxia relief dramatically inhibits tumor growth and liver metastasis in an HT-29 colon cancer mouse model. In addition, the O@PFOB@PGL NPs could serve as a bimodal contrast agent to enhance fluorescence and CT imaging, visualizing nanoparticle accumulation to guide the subsequent laser irradiation for precise PDT.
光动力疗法（PDT）在结肠癌治疗方面显示出巨大潜力。然而，实际上，使用纳米载体同时共递送光敏剂和氧气以改善针对与肿瘤转移密切相关的PDT诱导的缺氧的光动力疗法是一项巨大挑战。因此，提出了一种有效的策略，基于将全氟辛基溴（PFOB）液体超声分散到预先形成的卟啉接枝脂质（PGL）纳米颗粒（NPs）中，开发一种氧自补充的PDT纳米载体，该纳米颗粒具有38.5%的高卟啉负载量，随后捕获氧气。有趣的是，PGL NPs中卟啉和烷基链的有序排列模式不仅保证了单线态氧生成的高效性，还减少了卟啉的荧光损失，使PGL NPs具有高荧光性。更重要的是，由于PGL和PFOB分子之间的强疏水相互作用，PFOB液体以98.15%的超高负载量稳定在PGL NPs内部，促进了有效的氧气递送。体外和体内结果均表明，所获得的O@PFOB@PGL NPs可作为一个突出的氧库，无需外部刺激即可有效地向缺氧肿瘤中补充氧气，有利于增强单线态氧生成、缓解缺氧以及随后下调COX-2表达。结果，在HT-29结肠癌小鼠模型中，使用O@PFOB@PGL NPs缓解缺氧显著抑制了肿瘤生长和肝转移。此外，O@PFOB@PGL NPs可作为一种双模态造影剂增强荧光和CT成像，可视化纳米颗粒的聚集，以指导随后的激光照射进行精确的光动力疗法。
