Hyaluronic Acid-modified Manganese-chelated Dendrimer-entrapped Gold Nanoparticles for the Targeted CT/MR Dual-mode Imaging of Hepatocellular Carcinoma

Overview

Journal Sci Rep

Specialty Science

Date 2016 Sep 23

PMID 27653258

Citations 10

Authors

Ruizhi Wang

Yu Luo

Shuohui Yang

Jiang Lin

Dongmei Gao

Yan Zhao

Jinguo Liu

Xiangyang Shi

Xiaolin Wang

Affiliations

Soon will be listed here.

Abstract

Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. The early and effective diagnosis has always been desired. Herein, we present the preparation and characterization of hyaluronic acid (HA)-modified, multifunctional nanoparticles (NPs) targeting CD44 receptor-expressing cancer cells for computed tomography (CT)/magnetic resonance (MR) dual-mode imaging. We first modified amine-terminated generation 5 poly(amidoamine) dendrimers (G5.NH) with an Mn chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), fluorescein isothiocyanate (FI), and HA. Then, gold nanoparticles (AuNPs) were entrapped within the above raw product, denoted as G5.NH-FI-DOTA-HA. The designed multifunctional NPs were formed after further Mn chelation and purification and were denoted as {(Au)G5.NH-FI-DOTA(Mn)-HA}. These NPs were characterized via several different techniques. We found that the {(Au)G5.NH-FI-DOTA(Mn)-HA} NPs exhibited good water dispersibility, stability under different conditions, and cytocompatibility within a given concentration range. Because both AuNPs and Mn were present in the product, {(Au)G5.NH-FI-DOTA(Mn)-HA} displayed a high X-ray attenuation intensity and favorable r relaxivity, which are advantageous properties for targeted CT/MR dual-mode imaging. This approach was used to image HCC cells in vitro and orthotopically transplanted HCC tumors in a unique in vivo model through the CD44 receptor-mediated endocytosis pathway. This work introduces a novel strategy for preparing multifunctional NPs via dendrimer nanotechnology.

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References

Chen Q, Li K, Wen S, Liu H, Peng C, Cai H . Targeted CT/MR dual mode imaging of tumors using multifunctional dendrimer-entrapped gold nanoparticles. Biomaterials. 2013; 34(21):5200-9. DOI: 10.1016/j.biomaterials.2013.03.009. View

Krishnamurthy R, Hernandez A, Kavuk S, Annam A, Pimpalwar S . Imaging the central conducting lymphatics: initial experience with dynamic MR lymphangiography. Radiology. 2014; 274(3):871-8. DOI: 10.1148/radiol.14131399. View

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136(5):E359-86. DOI: 10.1002/ijc.29210. View

Sala E, Rockall A, Rangarajan D, Kubik-Huch R . The role of dynamic contrast-enhanced and diffusion weighted magnetic resonance imaging in the female pelvis. Eur J Radiol. 2010; 76(3):367-85. DOI: 10.1016/j.ejrad.2010.01.026. View

Kim S, Kamaya A, Willmann J . CT perfusion of the liver: principles and applications in oncology. Radiology. 2014; 272(2):322-44. PMC: 4263626. DOI: 10.1148/radiol.14130091. View

Yang H, Cai W, Xu L, Lv X, Qiao Y, Li P . Nanobubble-Affibody: Novel ultrasound contrast agents for targeted molecular ultrasound imaging of tumor. Biomaterials. 2014; 37:279-88. DOI: 10.1016/j.biomaterials.2014.10.013. View

Weissleder R, Pittet M . Imaging in the era of molecular oncology. Nature. 2008; 452(7187):580-9. PMC: 2708079. DOI: 10.1038/nature06917. View

Yang C, He Y, Zhang H, Liu Y, Wang W, Du Y . Selective killing of breast cancer cells expressing activated CD44 using CD44 ligand-coated nanoparticles in vitro and in vivo. Oncotarget. 2015; 6(17):15283-96. PMC: 4558151. DOI: 10.18632/oncotarget.3681. View

Lee J, Huh Y, Jun Y, Seo J, Jang J, Song H . Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging. Nat Med. 2006; 13(1):95-9. DOI: 10.1038/nm1467. View

10.

Barreto J, OMalley W, Kubeil M, Graham B, Stephan H, Spiccia L . Nanomaterials: applications in cancer imaging and therapy. Adv Mater. 2011; 23(12):H18-40. DOI: 10.1002/adma.201100140. View

11.

Yamada Y, Hashida M, Harashima H . Hyaluronic acid controls the uptake pathway and intracellular trafficking of an octaarginine-modified gene vector in CD44 positive- and CD44 negative-cells. Biomaterials. 2015; 52:189-98. DOI: 10.1016/j.biomaterials.2015.02.027. View

12.

Ream J, Doshi A, Lala S, Kim S, Rusinek H, Chandarana H . High Spatiotemporal Resolution Dynamic Contrast-Enhanced MR Enterography in Crohn Disease Terminal Ileitis Using Continuous Golden-Angle Radial Sampling, Compressed Sensing, and Parallel Imaging. AJR Am J Roentgenol. 2015; 204(6):W663-9. DOI: 10.2214/AJR.14.13674. View

13.

Weissleder R . Molecular imaging in cancer. Science. 2006; 312(5777):1168-71. DOI: 10.1126/science.1125949. View

14.

Pagel M . The hope and hype of multimodality imaging contrast agents. Nanomedicine (Lond). 2011; 6(6):945-8. DOI: 10.2217/nnm.11.63. View

15.

Liu Y, Chen Z, Liu C, Yu D, Lu Z, Zhang N . Gadolinium-loaded polymeric nanoparticles modified with Anti-VEGF as multifunctional MRI contrast agents for the diagnosis of liver cancer. Biomaterials. 2011; 32(22):5167-76. DOI: 10.1016/j.biomaterials.2011.03.077. View

16.

Cao Y, He Y, Liu H, Luo Y, Shen M, Xia J . Targeted CT imaging of human hepatocellular carcinoma using low-generation dendrimer-entrapped gold nanoparticles modified with lactobionic acid. J Mater Chem B. 2020; 3(2):286-295. DOI: 10.1039/c4tb01542h. View

17.

Weber J, Haberkorn U, Mier W . Cancer stratification by molecular imaging. Int J Mol Sci. 2015; 16(3):4918-46. PMC: 4394457. DOI: 10.3390/ijms16034918. View

18.

Manniesing R, Oei M, van Ginneken B, Prokop M . Quantitative Dose Dependency Analysis of Whole-Brain CT Perfusion Imaging. Radiology. 2015; 278(1):190-7. DOI: 10.1148/radiol.2015142230. View

19.

Sahoo B, Devi K, Dutta S, Maiti T, Pramanik P, Dhara D . Biocompatible mesoporous silica-coated superparamagnetic manganese ferrite nanoparticles for targeted drug delivery and MR imaging applications. J Colloid Interface Sci. 2014; 431:31-41. DOI: 10.1016/j.jcis.2014.06.003. View

20.

Bandula S, Punwani S, Rosenberg W, Jalan R, Hall A, Dhillon A . Equilibrium contrast-enhanced CT imaging to evaluate hepatic fibrosis: initial validation by comparison with histopathologic sampling. Radiology. 2014; 275(1):136-43. DOI: 10.1148/radiol.14141435. View