Key Jaehong, Dhawan Deepika, Cooper Christy L, Knapp Deborah W, Kim Kwangmeyung, Kwon Ick Chan, Choi Kuiwon, Park Kinam, Decuzzi Paolo, Leary James F
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA; Department of Biomedical Engineering, Yonsei University, Wonju, Republic of Korea.
School of Veterinary Medicine-Department of Basic Medical Sciences, Purdue University, West Lafayette.
Int J Nanomedicine. 2016 Aug 29;11:4141-55. doi: 10.2147/IJN.S109494. eCollection 2016.
While current imaging modalities, such as magnetic resonance imaging (MRI), computed tomography, and positron emission tomography, play an important role in detecting tumors in the body, no single-modality imaging possesses all the functions needed for a complete diagnostic imaging, such as spatial resolution, signal sensitivity, and tissue penetration depth. For this reason, multimodal imaging strategies have become promising tools for advanced biomedical research and cancer diagnostics and therapeutics. In designing multimodal nanoparticles, the physicochemical properties of the nanoparticles should be engineered so that they successfully accumulate at the tumor site and minimize nonspecific uptake by other organs. Finely altering the nano-scale properties can dramatically change the biodistribution and tumor accumulation of nanoparticles in the body. In this study, we engineered multimodal nanoparticles for both MRI, by using ferrimagnetic nanocubes (NCs), and near infrared fluorescence imaging, by using cyanine 5.5 fluorescence molecules. We changed the physicochemical properties of glycol chitosan nanoparticles by conjugating bladder cancer-targeting peptides and loading many ferrimagnetic iron oxide NCs per glycol chitosan nanoparticle to improve MRI contrast. The 22 nm ferrimagnetic NCs were stabilized in physiological conditions by encapsulating them within modified chitosan nanoparticles. The multimodal nanoparticles were compared with in vivo MRI and near infrared fluorescent systems. We demonstrated significant and important changes in the biodistribution and tumor accumulation of nanoparticles with different physicochemical properties. Finally, we demonstrated that multimodal nanoparticles specifically visualize small tumors and show minimal accumulation in other organs. This work reveals the importance of finely modulating physicochemical properties in designing multimodal nanoparticles for bladder cancer imaging.
虽然当前的成像方式,如磁共振成像(MRI)、计算机断层扫描和正电子发射断层扫描,在检测体内肿瘤方面发挥着重要作用,但没有单一模态成像具备完整诊断成像所需的所有功能,如空间分辨率、信号灵敏度和组织穿透深度。因此,多模态成像策略已成为先进生物医学研究以及癌症诊断与治疗的有前景的工具。在设计多模态纳米颗粒时,应设计纳米颗粒的物理化学性质,使其成功在肿瘤部位积聚,并将其他器官的非特异性摄取降至最低。精细改变纳米尺度的性质可显著改变纳米颗粒在体内的生物分布和肿瘤积聚情况。在本研究中,我们通过使用亚铁磁性纳米立方体(NCs)设计用于MRI的多模态纳米颗粒,并通过使用花菁5.5荧光分子设计用于近红外荧光成像的多模态纳米颗粒。我们通过连接膀胱癌靶向肽并在每个糖基壳聚糖纳米颗粒中负载许多亚铁磁性氧化铁NCs来改变糖基壳聚糖纳米颗粒的物理化学性质,以提高MRI对比度。通过将22纳米的亚铁磁性NCs封装在改性壳聚糖纳米颗粒中,使其在生理条件下稳定。将多模态纳米颗粒与体内MRI和近红外荧光系统进行了比较。我们证明了具有不同物理化学性质的纳米颗粒在生物分布和肿瘤积聚方面存在显著且重要的变化。最后,我们证明多模态纳米颗粒能够特异性地可视化小肿瘤,并且在其他器官中的积聚极少。这项工作揭示了在设计用于膀胱癌成像的多模态纳米颗粒时精细调节物理化学性质的重要性。