School of Materials Science and Engineering, Gwangju Institute of Science and Technology, 261 Cheomdan-gwagiro, Buk-gu, Gwangju 61005, Republic of Korea.
Department of Radiology, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Gwangju 61469, Republic of Korea.
J Control Release. 2016 Aug 28;236:90-9. doi: 10.1016/j.jconrel.2016.06.031. Epub 2016 Jun 25.
Developing novel nanotheranostic agent using only clinically approved materials is highly desirable and challenging. In this study, we combined three clinically approved materials, Prussian blue (PB), serum albumin (BSA), and indocyanine green (ICG), by a simple and biocompatible method to prepare a multifunctional theranostic PB-BSA-ICG nanoparticle. The multifunctional nanoparticle system could provide dual mode magnetic resonance (MR) and near infrared (NIR) fluorescence imaging as well as combined photothermal and photodynamic (PTT-PDT) therapy in response to a single NIR laser. This nanoparticle showed an excellent stability in physiological solutions and could suppress the photo-instability of ICG. In the absence of light, the nanoparticles showed no cytotoxicity, but significant cell death was induced through combined PTT-PDT effect after irradiation with NIR laser light. A high tumor accumulation and minimal nonspecific uptake by other major organs of PB-BSA-ICG nanoparticle were observed in vivo, analyzed by T1-weighted MR and NIR fluorescence bimodal imaging in tumor xenograft mice after intravenous injection. The nanoparticles efficiently suppressed the tumor growth through combinatorial phototherapy with no tumor recurrence upon a single NIR laser irradiation. These results demonstrated that PB-BSA-ICG is potentially an interesting nanotheranostic agent for imaging guided cancer therapy by overcoming the limitations of each technology and enhancing the therapeutic efficiency as well as reducing side effects.
仅使用临床批准的材料开发新型的纳米诊疗试剂是非常可取和具有挑战性的。在本研究中,我们通过一种简单且生物相容的方法将三种临床批准的材料普鲁士蓝(PB)、血清白蛋白(BSA)和吲哚菁绿(ICG)结合在一起,制备了一种多功能诊疗 PB-BSA-ICG 纳米粒子。该多功能纳米粒子系统可提供双模式磁共振(MR)和近红外(NIR)荧光成像以及光热和光动力(PTT-PDT)联合治疗,以响应单一 NIR 激光。该纳米粒子在生理溶液中表现出优异的稳定性,并能抑制 ICG 的光不稳定性。在没有光的情况下,纳米粒子没有细胞毒性,但在 NIR 激光照射后通过联合 PTT-PDT 效应,可诱导显著的细胞死亡。静脉注射后,通过 T1 加权 MR 和肿瘤异种移植小鼠的近红外荧光双模式成像分析,观察到 PB-BSA-ICG 纳米粒子具有高肿瘤积累和最小的非特异性摄取其他主要器官。通过组合光疗,纳米粒子有效地抑制了肿瘤生长,单次 NIR 激光照射后无肿瘤复发。这些结果表明,PB-BSA-ICG 可能是一种有前途的用于成像引导癌症治疗的纳米诊疗试剂,它克服了每种技术的局限性,提高了治疗效率,同时减少了副作用。