Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, and ‡MoE Key Laboratory for Biomedical Photonics, Department of Biomedical Engineering, Huazhong University of Science and Technology , Wuhan 430074, China.
ACS Nano. 2014 May 27;8(5):4334-47. doi: 10.1021/nn405989n. Epub 2014 May 1.
Current treatment of advanced-stage nasopharyngeal carcinoma (NPC) is not satisfactory. Targeted therapies offer hope for extending survival. Here, we developed simple, robust, and NPC-specific therapeutic lipid nanoparticles based on a fusion peptide, α-NTP, made up of an amphipathic α-helical peptide (α-peptide) linked to an NPC-specific therapeutic peptide (NTP). We found that α-NTP not only retained the sub-30 nm nanostructure-controlling ability of the α-peptide but also displayed the enhanced NPC-targeting ability of the NTP, in which the α-peptide accelerated the uptake of the NTP by NPC cells, with a 4.8-fold increase. Following uptake, α-NTP-based lipid nanoparticles (α-NTP-LNs) exerted coordinated cytotoxicity by inducing cell death via apoptosis and autophagy. In vivo and ex vivo optical imaging data showed that systemically administered α-NTP-LNs efficiently accumulated in the NPC xenograft tumor and displayed high contrast between tumor and normal tissues, which was further confirmed by flow cytometry that there had been a 13-fold uptake difference between tumor cells and hepatocytes. More importantly, the therapeutic efficacy of α-NTP-LNs was specific to NPC xenograft formed with 5-8F cells but not to fibrosarcoma xenograft formed with HT1080 cells in vivo. The growth of 5-8F tumors was significantly inhibited by α-NTP-LNs, with more than 85% inhibition relative to control groups (e.g., α-NTP and PBS treatment). In a lung metastasis model of NPC, survival was significantly improved by α-NTP-LN treatment. In a word, these excellent properties of α-NTP-LNs worked in sync and synergistically, maximizing the therapeutic efficacy of α-NTP-LNs against NPC and its metastasis.
目前，晚期鼻咽癌（NPC）的治疗效果并不令人满意。靶向治疗为延长生存期带来了希望。在这里，我们基于融合肽α-NTP 开发了简单、稳健且具有 NPC 特异性的治疗性脂质纳米粒，该融合肽由一个两亲性的 α-螺旋肽（α-肽）与一个 NPC 特异性治疗肽（NTP）连接而成。我们发现，α-NTP 不仅保留了 α-肽的亚 30nm 纳米结构控制能力，而且还表现出了 NTP 增强的 NPC 靶向能力，其中 α-肽加速了 NTP 被 NPC 细胞的摄取，摄取量增加了 4.8 倍。摄取后，基于 α-NTP 的脂质纳米粒（α-NTP-LN）通过诱导细胞凋亡和自噬来发挥协同细胞毒性作用。体内和离体光学成像数据表明，系统给予的 α-NTP-LN 能够有效地在 NPC 异种移植肿瘤中积累，并在肿瘤和正常组织之间显示出高对比度，这进一步通过流式细胞术证实，肿瘤细胞与肝细胞之间的摄取差异有 13 倍。更重要的是，α-NTP-LN 的治疗效果是特异性的，仅针对由 5-8F 细胞形成的 NPC 异种移植瘤，而对由 HT1080 细胞形成的纤维肉瘤异种移植瘤无效。α-NTP-LN 显著抑制了 5-8F 肿瘤的生长，与对照组（例如，α-NTP 和 PBS 处理）相比，抑制率超过 85%。在 NPC 的肺转移模型中，α-NTP-LN 治疗显著提高了存活率。总之，α-NTP-LN 的这些优异特性协同作用，最大限度地提高了 α-NTP-LN 对 NPC 及其转移的治疗效果。
