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

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.

Overview on natural hydrophilic polysaccharide polymers in drug delivery

“…In addition, researchers reported that on dual‐modality, chitosan nanospheres improved their function as Magnetic resonance imaging (MRI) agents as well as optical imaging agents with near infrared fluorescence (NIRF) probes, like cyanine 5.5 [Cy5.5] and positron emission tomography imaging agents. In addition, they performed in vivo dual‐modality imaging, probing specific tumor areas by applying the nanoparticles …”

Multicomponent, Tumor-Homing Chitosan Nanoparticles for Cancer Imaging and Therapy

“…For example, 22-nm iron oxide nanocubes, Cy5.5 and a bladder cancer-targeting peptide (CSNRDARRC) can be combined in modified glycol chitosan nanoparticles by using hydrophobic moieties. Interestingly, the resulting multicomponent system changes not only the visualization capability, but also the biodistribution of the nanoparticles in the body, changing RES uptake features in organs and enhancing tumor accumulation (Figure 6) [9]. …”

“…Surface coverage by the targeting ligands may result in non-specific accumulation of nanoparticles in the liver or spleen via RES recognition. Nevertheless, active targeting through in vitro tests usually demonstrates higher internalization of the nanoparticles into specific cancer cells via receptor-mediated endocytosis [9]. …”

“…( A ) Chemical structures and schematic diagram of glycol chitosan conjugated to hydrophobic 5β-cholanic acid and bladder cancer-targeting peptide (CSNRDARRC) and physically loaded with iron oxide nanocubes (NCs); ( B ) the combination demonstrated a specific tumor-targeting capability with minimized accumulation in other organs: ( a ) after NP administration and ( b ) before NP administration (Adapted with permission from [9]. Copyright 2016 DOVE Medical Press).…”

“…For example, fluorescent imaging can be applied to fluorescent image-guided surgery in humans. Furthermore, fluorescent-labeled iron oxide nanoparticles enable whole-body MR imaging and fluorescent image-guided delineation of the tumor margin [9,10]. …”