Molecular Imaging and Therapy Branch, National Cancer Center, 323 Ilsan-ro, Goyang-si, Gyeonggi-do 410-769, Korea;
Quant Imaging Med Surg. 2013 Jun;3(3):132-40. doi: 10.3978/j.issn.2223-4292.2013.06.03.
We have developed an indocyanine green-loaded perfluorocarbon (ICG/PFCE) nanoemulsion as a multifunctional theranostic nanomedicine which enables not only (19)F magnetic resonance (MR)/near-infrared fluorescence (NIRF) bimodal imaging but also subsequent photodynamic/photothermal dual therapy of cancer. The hydrodynamic size of ICG/PFCE nanoemulsions was 164.2 nm. The stability of indocyanine green (ICG) in aqueous solution was significantly improved when loaded on perfluorocarbon nanoemulsions. In addition, ICG/PFCE nanoemulsions showed good dispersion stability in aqueous media containing 10% fetal bovine serum, for at least 14 days. (19)F-MRI of ICG/PFCE nanoemulsions showed that the signal intensity increased with increasing nanoemulsion concentration with no signal observed from the surrounding background. Using NIRF imaging with perfluorocarbon nanoemulsion alone, without ICG, did not produce NIRF, while clear and bright fluorescent images were obtained with ICG/PFCE nanoemulsions at 10-µM ICG equivalent. The capacity of ICG-loaded nanoemulsions to generate heat following light irradiation by using an 810-nm laser was comparable to that of free ICG, while singlet oxygen generation of ICG-loaded nanoemulsions was significantly better than that of free ICG. In vitro cytotoxicity tests and fluorescence microscopy confirmed biocompatibility of the nanoemulsion. Upon light irradiation, U87MG glioblastoma cells incubated with ICG/PFCE nanoemulsions underwent necrotic cell death. The therapeutic mechanism during light illumination appears to be mainly due to the photodynamic effect at lower ICG concentrations, whilst the photothermal effect became more obvious at increased ICG concentrations, enabling combined photodynamic/photothermal therapy of cancer cells.
我们开发了一种载有吲哚菁绿的全氟碳（ICG/PFCE）纳米乳液，作为一种多功能治疗性纳米医学，不仅能够进行（19）F 磁共振（MR）/近红外荧光（NIRF）双模式成像，还能够随后对癌症进行光动力/光热双重治疗。ICG/PFCE 纳米乳液的水动力学尺寸为 164.2nm。当载于全氟碳纳米乳液中时，吲哚菁绿（ICG）在水溶液中的稳定性得到显著提高。此外，ICG/PFCE 纳米乳液在含有 10%胎牛血清的水介质中具有良好的分散稳定性，至少可稳定 14 天。（19）F-MRI 显示，随着纳米乳液浓度的增加，信号强度增加，而周围背景没有观察到信号。使用单独的全氟碳纳米乳液进行 NIRF 成像，没有 ICG，不会产生 NIRF，而用 10-µM ICG 等效浓度的 ICG/PFCE 纳米乳液则可获得清晰明亮的荧光图像。用光照射后，载有 ICG 的纳米乳液产生热量的能力与游离 ICG 相当，而载有 ICG 的纳米乳液产生单线态氧的能力明显优于游离 ICG。体外细胞毒性试验和荧光显微镜证实了纳米乳液的生物相容性。在光照下，用 ICG/PFCE 纳米乳液孵育的 U87MG 神经胶质瘤细胞发生坏死性细胞死亡。在光照期间的治疗机制似乎主要是由于较低浓度的 ICG 产生光动力效应，而随着 ICG 浓度的增加，光热效应变得更加明显，从而能够对癌细胞进行联合光动力/光热治疗。
