Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan.
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan; Department of Surgery, Hsinchu Mackay Memorial Hospital, Hsinchu City 30071, Taiwan.
J Control Release. 2020 Dec 10;328:87-99. doi: 10.1016/j.jconrel.2020.08.038. Epub 2020 Aug 26.
The combination of photothermal and photodynamic therapy (PTT/PDT) shows pronounced potential as a prominent therapeutic strategy for tumor treatment. However, the efficacy is limited by insufficient tumor-targeted delivery of PTT and PDT reagents and the hypoxic nature of the tumor microenvironment. To overcome these limitations, tumor acidity-responsive lipid membrane-enclosed perfluorooctyl bromide oil droplet nanoparticles (NPs) surface modified with N-acetyl histidine-modified D-α-tocopheryl polyethylene glycol 1000 succinate (PFOB@IMHNPs) were developed, capable of co-delivering oxygen, IR780 (a photothermal agent) and mTHPC (a photodynamic sensitizer) into tumors. Through self-sufficient oxygen transportation in combination with promotion of cellular uptake upon acid-triggered generation of surface positive charge, the PFOB@IMHNPs effectively delivered IR780 and mTHPC and produced singlet oxygen within hypoxic TRAMP-C1 cells following exposure to irradiation at 660 nm. This led to effective killing of hypoxic cancer cells in vitro. Importantly, when irradiation at 808 and 660 nm was carried out, PT/PD combination therapy utilizing PFOB@IMHNPs dramatically suppressed the growth of TRAMP-C1 tumors through effective tumor-targeted cargo delivery and relief of tumor hypoxia. Our results suggest the high potential of the PFOB@IMHNPs developed in this study in clinical application for cancer treatment.
光热和光动力疗法（PTT/PDT）的联合应用显示出作为肿瘤治疗的一种突出治疗策略的显著潜力。然而，其疗效受到 PTT 和 PDT 试剂的肿瘤靶向递送不足以及肿瘤微环境的缺氧性质的限制。为了克服这些限制，开发了肿瘤酸度响应性脂质膜封闭的全氟辛基溴油滴纳米颗粒（NPs），其表面修饰有 N-乙酰组氨酸修饰的 D-α-生育酚聚乙二醇 1000 琥珀酸（PFOB@IMHNPs），能够将氧气、IR780（一种光热剂）和 mTHPC（一种光动力敏化剂）共同递送到肿瘤中。通过自充足的氧气运输，并在酸性触发表面正电荷产生时促进细胞摄取，PFOB@IMHNPs 有效地递送至 IR780 和 mTHPC，并在接受 660nm 照射后在缺氧的 TRAMP-C1 细胞内产生单线态氧。这导致体外缺氧癌细胞的有效杀伤。重要的是，当在 808 和 660nm 进行照射时，利用 PFOB@IMHNPs 的 PT/PD 联合治疗通过有效的肿瘤靶向货物递送和缓解肿瘤缺氧，显著抑制了 TRAMP-C1 肿瘤的生长。我们的研究结果表明，本研究中开发的 PFOB@IMHNPs 在癌症治疗的临床应用中具有很大的潜力。
