Multicomponent, peptide-targeted glycol chitosan nanoparticles containing ferrimagnetic iron oxide nanocubes for bladder cancer multimodal imaging

Jaehong Key,1,2 Deepika Dhawan,3 Christy L Cooper,3,4 Deborah W Knapp,3 Kwangmeyung Kim,5 Ick Chan Kwon,5 Kuiwon Choi,5 Kinam Park,1,6 Paolo Decuzzi,7–9 James F Leary1,3,41Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA; 2Department of Biomedical Engineering, Yonsei University, Wonju, Republic of Korea; 3School of Veterinary Medicine-Department of Basic Medical Sciences, Purdue University, West Lafayette, 4Birck Nanotechnology Center at Discovery Park, Purdue University, West Lafayette, IN, USA; 5Biomedical Research Center, Korea Institute of Science and Technology, Sungbook-Gu, Seoul, Republic of Korea; 6Department of Pharmaceutics, Purdue University, West Lafayette, IN, 7Department of Translational Imaging, 8Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX USA; 9Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia (IIT), Genova, Italy Abstract: 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.Keywords: MRI, NIRF, multimodal imaging, chitosan, iron oxide, bladder cance