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Key, Jaehong,Dhawan, Deepika,Cooper, Christy L,Knapp, Deborah W,Kim, Kwangmeyung,Kwon, Ick Chan,Choi, Kuiwon,Park, Kinam,Decuzzi, Paolo,Leary, James F Dove Medical Press 2016 International journal of nanomedicine Vol.11 No.-
<P>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.</P>
Cervadoro, Antonio,Cho, Minjung,Key, Jaehong,Cooper, Christy,Stigliano, Cinzia,Aryal, Santosh,Brazdeikis, Audrius,Leary, James F.,Decuzzi, Paolo American Chemical Society 2014 ACS APPLIED MATERIALS & INTERFACES Vol.6 No.15
<P/><P>Iron oxide nanoparticles (IOs) are intrinsically theranostic agents that could be used for magnetic resonance imaging (MRI) and local hyperthermia or tissue thermal ablation. Yet, effective hyperthermia and high MR contrast have not been demonstrated within the same nanoparticle configuration. Here, magnetic nanoconstructs are obtained by confining multiple, ∼ 20 nm nanocubes (NCs) within a deoxy-chitosan core. The resulting nanoconstructs—magnetic nanoflakes (MNFs)—exhibit a hydrodynamic diameter of 156 ± 3.6 nm, with a polydispersity index of ∼0.2, and are stable in PBS up to 7 days. Upon exposure to an alternating magnetic field of 512 kHz and 10 kA m<SUP>–1</SUP>, MNFs provide a specific absorption rate (SAR) of ∼75 W g<SUB>Fe</SUB><SUP>–1</SUP>, which is 4–15 times larger than that measured for conventional IOs. Moreover, the same nanoconstructs provide a remarkably high transverse relaxivity of ∼500 (mM s)<SUP>−1</SUP>, at 1.41T. MNFs represent a first step toward the realization of nanoconstructs with superior relaxometric and ablation properties for more effective theranostics.</P>
Paramagnetic Gd<sup>3+</sup> labeled red blood cells for magnetic resonance angiography
Aryal, S.,Stigliano, C.,Key, J.,Ramirez, M.,Anderson, J.,Karmonik, C.,Fung, S.,Decuzzi, P. IPC Science and Technology Press 2016 Biomaterials Vol.98 No.-
<P>Despite significant advances in contrast enhanced-magnetic resonance angiography, the lack of truly blood-pool agents with long circulating property is limiting the clinical impact of this imaging technique. The terminal half-life for blood elimination of most small molecular weight gadolinium (Gd) based extracellular fluid agents is about 1.5 h when administered intravenously to subjects with normal renal function. The small size of these extracellular fluid agents does not prevent them from extravasating, especially from damaged vessels which are generally hyperpermeable. Therefore, the development of novel, clinically relevant blood pool contrast agents is critically needed to improve outcomes in the prevention, detection, and treatment of vascular diseases. We have demonstrated the fusion strategies in which the Gd-liposome without any stealth property radically fuses with red blood cells (RBCs) forming MR glowing Gd-RBC with the order of magnitude enhancements in circulation half-life (t(1/2) = 50 h) and r(1) relaxivity (r(1) = 19.0 mM(-1) s(-1)) of Gd. The in vivo contrast enhancement of Gd-RBC was studied by using 3T clinical MR scanner for extended period of time, which clearly visualized the abdominal aorta. In summary, the vascular delivery of blood pool agents may benefit from carriage by RBCs because it naturally stays within the vascular lumen. (C) 2016 Elsevier Ltd. All rights reserved.</P>
van de Ven, A.L.,Kim, P.,Haley, O.,Fakhoury, J.R.,Adriani, G.,Schmulen, J.,Moloney, P.,Hussain, F.,Ferrari, M.,Liu, X.,Yun, S.H.,Decuzzi, P. Elsevier Science Publishers 2012 Journal of controlled release Vol.158 No.1
Nanoparticles for cancer therapy and imaging are designed to accumulate in the diseased tissue by exploiting the Enhanced Permeability and Retention (EPR) effect. This limits their size to about 100nm. Here, using intravital microscopy and elemental analysis, we compare the in vivo localization of particles with different geometries and demonstrate that plateloid particles preferentially accumulate within the tumor vasculature at unprecedented levels, independent of the EPR effect. In melanoma-bearing mice, 1000x400nm plateloid particles adhered to the tumor vasculature at about 5% and 10% of the injected dose per gram organ (ID/g) for untargeted and RGD-targeted particles respectively, and exhibited the highest tumor-to-liver accumulation ratios (0.22 and 0.35). Smaller and larger plateloid particles, as well as cylindroid particles, were more extensively sequestered by the liver, spleen, and lungs. Plateloid particles appeared well-suited for taking advantage of hydrodynamic forces and interfacial interactions required for efficient tumoritropic accumulation, even without using specific targeting ligands.