In vitro and in vivo magnetic resonance imaging with chlorotoxin-conjugated superparamagnetic nanoprobes for targeting hepatocarcinoma

Chen,Zhu; Xiao,En-Hua; Kang,Zhen; Zeng,Wen-Bin; Tan,Hui-Long; Li,Hua-Bing; Bian,Du-Jun; Shang,Quan-Liang

doi:10.3892/or.2016.4629

In vitro and in vivo magnetic resonance imaging with chlorotoxin-conjugated superparamagnetic nanoprobes for targeting hepatocarcinoma

Authors:
- Zhu Chen
- En-Hua Xiao
- Zhen Kang
- Wen-Bin Zeng
- Hui-Long Tan
- Hua-Bing Li
- Du-Jun Bian
- Quan-Liang Shang
View Affiliations

Affiliations: Department of Radiology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, P.R. China
Published online on: February 23, 2016 https://doi.org/10.3892/or.2016.4629
Pages: 3059-3067

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study aimed to assess the in vitro and in vivo magnetic resonance imaging (MRI) features of chlorotoxin (CTX)-conjugated superparamagnetic iron oxide (SPIO) nanoprobes. CTX-conjugated nanoprobes were composed of SPIO coated with polyethylene glycol (PEG) and conjugated with CTX. The nanoprobes were termed SPIO-PEG-CTX. MRI of the SPIO and SPIO-PEG-CTX solutions at a different concentration was performed with a 3.0-T MRI scanner (Philips Achieva 3.0T X Series; Phillips Healthcare, The Netherlands). Rabbit VX2 hepatocarcinoma was established by a traditional laparotomy method (injection of the tumor particles into the liver using a 15G syringe needle) following approval by the institutional animal care and use committee. Contrast-enhanced MRI of VX2 rabbits (n=8) was performed using the same MRI scanner with SPIO‑PEG-CTX solutions as the contrast agent. Data were analyzed with calibration curve and a paired t-test. The SPIO-PEG-CTX nanoparticles were successfully prepared. With increasing concentrations of the solutions, the MRI signal intensity was increased at T1WI, but decreased at T2WI, which were the same as that for SPIO. Rabbit VX2 carcinoma appeared as a low MRI signal at T1WI, and high at T2WI. After injection of the contrast agent, the MRI signal of carcinoma was decreased relative to that before injection at T2WI (1,161±331.5 vs. 1,346±300.5; P=0.004<0.05), while the signal of the adjacent normal hepatic tissues was unchanged (480.6±165.1 vs. 563.4±67.8; P=0.202>0.05). The SPIO-PEG-CTX nanoparticles showed MRI negative enhancement at T2WI and a targeting effect in liver cancer, which provides the theoretical basis for further study of the early diagnosis of hepatocellular carcinoma.

View Figures

View References

1	Kudo M: Hepatocellular carcinoma 2009 and beyond: From the surveillance to molecular targeted therapy. Oncology. 75(Suppl 1): S1–S12. 2008. View Article : Google Scholar
2	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
3	Obuz F, Oksüzler M, Seçil M, Sağol O, Karademir S and Astarcioğlu H: Efficiency of MR imaging in the detection of malignant liver lesions. Diagn Interv Radiol. 12:17–21. 2006.PubMed/NCBI
4	Bowman K and Leong KW: Chitosan nanoparticles for oral drug and gene delivery. Int J Nanomedicine. 1:117–128. 2006. View Article : Google Scholar
5	Cheng FY, Su CH, Yang YS, Yeh CS, Tsai CY, Wu CL, Wu MT and Shieh DB: Characterization of aqueous dispersions of Fe₃O₄ nanoparticles and their biomedical applications. Biomaterials. 26:729–738. 2005. View Article : Google Scholar
6	Le Renard PE, Lortz R, Senatore C, Rapin JP, Buchegger F, Petri-Fink A, Hofmann H, Doelker E and Jordan O: Magnetic and in vitro heating properties of implants formed in situ from injectable formulations and containing superparamagnetic iron oxide nanoparticles (SPIONs) embedded in silica microparticles for magnetically induced local hyperthermia. J Magn Magn Mater. 323:1054–1063. 2011. View Article : Google Scholar
7	Rosen JE, Chan L, Shieh DB and Gu FX: Iron oxide nanoparticles for targeted cancer imaging and diagnostics. Nanomedicine. 8:275–290. 2012.
8	Tassa C, Shaw SY and Weissleder R: Dextran-coated iron oxide nanoparticles: A versatile platform for targeted molecular imaging, molecular diagnostics, and therapy. Acc Chem Res. 44:842–852. 2011. View Article : Google Scholar : PubMed/NCBI
9	Nishie A, Tajima T, Ishigami K, Ushijima Y, Okamoto D, Hirakawa M, Nishihara Y, Taketomi A, Hatakenaka M, Irie H, et al: Detection of hepatocellular carcinoma (HCC) using super paramagnetic iron oxide (SPIO)-enhanced MRI: Added value of diffusion-weighted imaging (DWI). J Magn Reson Imaging. 31:373–382. 2010. View Article : Google Scholar : PubMed/NCBI
10	Tanimoto A and Kuribayashi S: Application of superparamagnetic iron oxide to imaging of hepatocellular carcinoma. Eur J Radiol. 58:200–216. 2006. View Article : Google Scholar : PubMed/NCBI
11	Veiseh O, Sun C, Gunn J, Kohler N, Gabikian P, Lee D, Bhattarai N, Ellenbogen R, Sze R, Hallahan A, et al: Optical and MRI multifunctional nanoprobe for targeting gliomas. Nano Lett. 5:1003–1008. 2005. View Article : Google Scholar : PubMed/NCBI
12	Sun C, Veiseh O, Gunn J, Fang C, Hansen S, Lee D, Sze R, Ellenbogen RG, Olson J and Zhang M: In vivo MRI detection of gliomas by chlorotoxin-conjugated superparamagnetic nano-probes. Small. 4:372–379. 2008. View Article : Google Scholar : PubMed/NCBI
13	Chen Z, Kang Z, Xiao EH, Tong M, Xiao YD and Li HB: Comparison of two different laparotomy methods for modeling rabbit VX2 hepatocarcinoma. World J Gastroenterol. 21:4875–4882. 2015. View Article : Google Scholar : PubMed/NCBI
14	Gupta AK and Gupta M: Cytotoxicity suppression and cellular uptake enhancement of surface modified magnetic nanoparticles. Biomaterials. 26:1565–1573. 2005. View Article : Google Scholar
15	Laurent S, Forge D, Port M, Roch A, Robic C, Vander Elst L and Muller RN: Magnetic iron oxide nanoparticles: Synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem Rev. 108:2064–2110. 2008. View Article : Google Scholar : PubMed/NCBI
16	Hyeon T: Chemical synthesis of magnetic nanoparticles. Chem Commun. 21:927–934. 2003. View Article : Google Scholar
17	Lichtinghagen R, Helmbrecht T, Arndt B and Böker KH: Expression pattern of matrix metalloproteinases in human liver. Eur J Clin Chem Clin Biochem. 33:65–71. 1995.PubMed/NCBI
18	Jacob A, Jing J, Lee J, Schedin P, Gilbert SM, Peden AA, Junutula JR and Prekeris R: Rab40b regulates trafficking of MMP2 and MMP9 during invadopodia formation and invasion of breast cancer cells. J Cell Sci. 126:4647–4658. 2013. View Article : Google Scholar : PubMed/NCBI
19	Wong JC, Chan SK, Schaeffer DF, Sagaert X, Lim HJ, Kennecke H, Owen DA, Suh KW, Kim YB and Tai IT: Absence of MMP2 expression correlates with poor clinical outcomes in rectal cancer, and is distinct from MMP1-related outcomes in colon cancer. Clin Cancer Res. 17:4167–4176. 2011. View Article : Google Scholar : PubMed/NCBI
20	Deshane J, Garner CC and Sontheimer H: Chlorotoxin inhibits glioma cell invasion via matrix metalloproteinase-2. J Biol Chem. 278:4135–4144. 2003. View Article : Google Scholar
21	Gryparis EC, Hatziapostolou M, Papadimitriou E and Avgoustakis K: Anticancer activity of cisplatin-loaded PLGA-mPEG nanoparticles on LNCaP prostate cancer cells. Eur J Pharm Biopharm. 67:1–8. 2007. View Article : Google Scholar : PubMed/NCBI
22	Gref R, Minamitake Y, Peracchia MT, Trubetskoy V, Torchilin V and Langer R: Biodegradable long-circulating polymeric nano-spheres. Science. 263:1600–1603. 1994. View Article : Google Scholar : PubMed/NCBI
23	Moghimi SM and Szebeni J: Stealth liposomes and long circulating nanoparticles: Critical issues in pharmacokinetics, opsonization and protein-binding properties. Prog Lipid Res. 42:463–478. 2003. View Article : Google Scholar : PubMed/NCBI
24	Gref R, Lück M, Quellec P, Marchand M, Dellacherie E, Harnisch S, Blunk T and Müller RH: 'Stealth' corona-core nanoparticles surface modified by polyethylene glycol (PEG): Influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids Surf B Biointerfaces. 18:301–313. 2000. View Article : Google Scholar : PubMed/NCBI
25	Juang JH, Wang JJ, Shen CR, Kuo CH, Chien YW, Kuo HY, Tsai ZT and Yen TC: Magnetic resonance imaging of transplanted mouse islets labeled with chitosan-coated superparamagnetic iron oxide nanoparticles. Transplant Proc. 42:2104–2108. 2010. View Article : Google Scholar : PubMed/NCBI
26	Ahmad T, Bae H, Rhee I, Chang Y, Lee J and Hong S: Particle size dependence of relaxivity for silica-coated iron oxide nanoparticles. Curr Appl Phys. 12:969–974. 2012. View Article : Google Scholar