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.
Bibliographical noteFunding Information:
This work was supported by the Intramural Research Program (Theragnosis) of KIST, the Christopher Columbus Foundation support to JFL, and a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No 2015R1C1A1A01052592). We would like to especially thank Patty I Bonney, Lindsey M Fourez, Jane C Stewart, and Carol Ann Dowell at Purdue University for their assistance with this work. We also express our appreciation to Dr Aaron Taylor of the Bindley Bioscience Imaging Facility, Dr Tom Talavage and Greg Tamer of the Purdue MRI facility at Purdue Research Park, Dr Debby Sherman and Mr Chia-Ping Huang of the Life Sciences Microscopy Facility at Purdue University for the TEM images, and Lisa Reece of the Bionano Facility in the Birck Nanotechnology Center who was supported in part by the Indiana Clinical and Translational Sciences Institute from the National Institutes of Health, National Center for Research Resources, Clinical and Translational Sciences Award.
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science
- Drug Discovery
- Organic Chemistry