Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, Department of Preventive Medicine, Third Military Medical University , Chongqing 400038, China.
Institute for Clean Energy and Advanced Materials, Southwest University , Chongqing 400715, China.
ACS Appl Mater Interfaces. 2016 Jul 13;8(27):17176-86. doi: 10.1021/acsami.6b05383. Epub 2016 Jun 29.
The integration of photodynamic therapy (PDT) with photothermal therapy (PTT) offers improved efficacy in cancer phototherapy. Herein, a PDT photosensitizer (IR-808) with cancer-targeting ability and near-infrared (NIR) sensitivity was chemically conjugated to both polyethylene glycol (PEG)- and branched polyethylenimine (BPEI)-functionalized nanographene oxide (NGO). Because the optimal laser wavelength (808 nm) of NGO for PTT is consistent with that of IR-808 for PDT, the IR-808-conjugated NGO sheets (NGO-808, 20-50 nm) generated both large amounts of reactive oxygen species (ROS) and local hyperthermia as a result of 808 nm laser irradiation. With PEG- and BPEI-modified NGO as the carrier, the tumor cellular uptake of NGO-808 exhibited higher efficacy than that of strongly hydrophobic free IR-808. Through evaluation with both human and mouse cancer cells, NGO-808 was demonstrated to provide significantly enhanced PDT and PTT effects compared to individual PDT using IR-808 or PTT using NGO. Furthermore, NGO-808 preferentially accumulated in cancer cells as mediated by organic-anion transporting polypeptides (OATPs) overexpressed in many cancer cells, providing the potential for highly specific cancer phototherapy. Using the targeting ability of NGO-808, in vivo NIR fluorescence imaging enabled tumors and their margins to be clearly visualized at 48 h after intravenous injection, providing a theranostic platform for imaging-guided cancer phototherapy. Remarkably, after a single injection of NGO-808 and 808 nm laser irradiation for 5 min, the tumors in two tumor xenograft models were ablated completely, and no tumor recurrence was observed. After treatment with NGO-808, no obvious toxicity was detected in comparison to control groups. Thus, high-performance cancer phototherapy with minimal side effects was afforded from synergistic PDT/PTT treatment and cancer-targeted accumulation of NGO-808.
光动力疗法 (PDT) 与光热疗法 (PTT) 的结合为癌症光疗提供了更高的疗效。在此，通过化学方法将具有癌症靶向能力和近红外 (NIR) 敏感性的 PDT 光敏剂 (IR-808) 与聚乙二醇 (PEG) 和支化聚乙烯亚胺 (BPEI) 功能化的纳米氧化石墨烯 (NGO) 进行偶联。由于 NGO 用于 PTT 的最佳激光波长 (808nm) 与用于 PDT 的 IR-808 的激光波长一致，因此，808nm 激光照射会导致 NGO-808 片产生大量的活性氧 (ROS) 和局部过热。由于 PEG 和 BPEI 改性的 NGO 作为载体，NGO-808 的肿瘤细胞摄取效率比强疏水性的游离 IR-808 更高。通过对人和小鼠癌细胞的评估，与单独使用 IR-808 进行 PDT 或单独使用 NGO 进行 PTT 相比，NGO-808 表现出显著增强的 PDT 和 PTT 效果。此外，NGO-808 通过在许多癌细胞中过度表达的有机阴离子转运多肽 (OATP) 介导，优先积聚在癌细胞中，为高度特异性的癌症光疗提供了潜力。利用 NGO-808 的靶向能力，在静脉注射后 48 小时，通过近红外荧光成像可以清楚地观察到肿瘤及其边缘，为成像引导的癌症光疗提供了一个治疗和诊断平台。值得注意的是，在两种肿瘤异种移植模型中，单次注射 NGO-808 和 808nm 激光照射 5 分钟后，肿瘤完全被消融，且未观察到肿瘤复发。与对照组相比，NGO-808 治疗后未观察到明显的毒性。因此，通过协同的 PDT/PTT 治疗和 NGO-808 的癌症靶向积累，实现了具有最小副作用的高效癌症光疗。
