Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-10T09:50:06.432Z Has data issue: false hasContentIssue false
  • English
  • Français

Effects of QDs@Gd3+-NGR on targeted fluorescence-magnetic resonance imaging and inhibition of pancreatic cancer cells

Published online by Cambridge University Press:  16 March 2020

Qinqin Yan ,
Lin Wang ,
Fengxiang Song ,
Yijun Zhang ,
Lu Gao ,
Fengjun Liu  and
Yuxin Shi
Qinqin Yan
Affiliation:
Department of Radiology, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China; and Shanghai Medical Imaging Institute, Fudan University, Shanghai 200032, China
Lin Wang
Affiliation:
Department of Radiology, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
Fengxiang Song
Affiliation:
Department of Radiology, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
Yijun Zhang
Affiliation:
Department of Radiology, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
Lu Gao
Affiliation:
Department of Radiology, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
Fengjun Liu*
Affiliation:
Department of Radiology, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
Yuxin Shi*
Affiliation:
Department of Radiology, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China; and Shanghai Medical Imaging Institute, Fudan University, Shanghai 200032, China
*
a)Address all correspondence to these authors. e-mail: liufengjun121@126.com
b)e-mail: shiyx828288@163.com
Get access

Abstract

Pancreatic cancer is currently one of the most lethal tumors because of delayed diagnosis and treatment. Aminopeptidase N (CD13/APN), expressed in pancreatic cancer cells, is closely related to the malignant biological behavior, for instance, angiogenesis formation, tumor proliferation, and metastasis. In this study, asparagine–glycine–arginine (Asn–Gly–Arg, NGR), selectively binding to CD13 receptor, was modified to construct a novel contrast agent of QDs@Gd3+-NGR for targeted diagnosis and treatment of pancreatic cancer. It consists of QDs-unit for fluorescence imaging, Gd3+-unit for magnetic resonance imaging (MRI), and NGR for binding to CD13 receptor. PANC-1 cells labeled by QDs@Gd3+-NGR showed significant red fluorescence and high intensity on fluorescence and MR imaging, respectively. Besides, it was confirmed that QDs@Gd3+-NGR could inhibit theproliferation, metastasis, and invasion of PANC-1 cells, and increase reactive oxygen species production and death rate in vitro. Reasonably, we believe the targeted contrast agent of QDs@Gd3+-NGR can sensitively detect pancreatic cancer via MR-fluorescence dual-modality imaging, and plays an active role in inhibition of tumor progression. The promising results in this study provide integration of diagnostic and therapeutic strategy for the management of pancreatic cancer in future.

Keywords

nanoprobepancreatic cancermagnetic resonance-fluorescent dual-modality imaginginhibition of tumor cells
Type
Article
Information
Journal of Materials Research , Volume 35 , Issue 6 , 30 March 2020 , pp. 591 - 599
Copyright
Copyright © Materials Research Society 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

c)

These authors contributed equally to this work.

References

Rahib, L., Smith, B.D., Aizenberg, R., Rosenzweig, A.B., Fleshman, J.M., and Matrisian, L.M.: Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 74, 2913 (2014).CrossRefGoogle ScholarPubMed
Zhang, Q., Zeng, L., Chen, Y., Lian, G., Qian, C., Chen, S., Li, J., and Huang, K.: Pancreatic cancer epidemiology, detection, and management. Gastroenterol. Res. Pract. 2016, 8962321 (2016).CrossRefGoogle ScholarPubMed
Nielsen, C.H., Jeppesen, T.E., Kristensen, L.K., Jensen, M.M., El Ali, H.H., Madsen, J., Wiinberg, B., Petersen, L.C., and Kjaer, A.: Pet imaging of tissue factor in pancreatic cancer using 64Cu-labeled active site inhibited factor VII. Nucl. Med. 57, 112 (2016).Google ScholarPubMed
Wang, Q., Yan, H., Jin, Y., Wang, Z., Huang, W., Qiu, J., Kang, F., Wang, K., Zhao, X., and Tian, J.: A novel plectin/integrin-targeted bispecific molecular probe for magnetic resonance/near-infrared imaging of pancreatic cancer. Biomaterials 183, 173 (2018).CrossRefGoogle ScholarPubMed
Pasqualini, R., Koivunen, E., Kain, R., Lahdenranta, J., Sakamoto, M., Stryhn, A., Ashmun, R.A., Shapiro, L.H., Arap, W., and Ruoslahti, E.: Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. Cancer Res. 60, 722 (2000).Google Scholar
Wang, X., Wang, Y-G., Chen, X-M., Wang, J-C., Zhang, X., and Zhang, Q.: NGR-modified micelles enhance their interaction with CD13-overexpressing tumor and endothelial cells. J. Controlled Release 139, 56 (2009).CrossRefGoogle ScholarPubMed
Plesniak, L.A., Salzameda, B., Hinderberger, H., Regan, E., Kahn, J., Mills, S.A., Teriete, P., Yao, Y., Jennings, P., Marassi, F., and Adams, J.A.: Structure and activity of CPNGRC: A modified CD13/APN peptidic homing motif. Chem. Biol. Drug Des. 75, 551 (2010).CrossRefGoogle ScholarPubMed
Luo, L-M., Huang, Y., Zhao, B-X., Zhao, X., Duan, Y., Du, R., Yu, K-F., Song, P., Zhao, Y., Zhang, X., and Zhang, Q.: Anti-tumor and anti-angiogenic effect of metronomic cyclic NGR-modified liposomes containing paclitaxel. Biomaterials 34, 1102 (2013).CrossRefGoogle ScholarPubMed
Corti, A. and Curnis, F.: Tumor vasculature targeting through NGR peptide-based drug delivery systems. Curr. Pharm. Biotechnol. 12, 1128 (2011).CrossRefGoogle ScholarPubMed
Wang, W-X., Zhen, L., and Lan, X-L.: Quantum dot-based simultaneous multicolor imaging. Mol. Imaging Biol. (2019). Available at: https://doi.org/10.1007/s11307-019-01432-4 (accessed September 16, 2019).CrossRefGoogle ScholarPubMed
Di Matteo, P., Arrigoni, G.L., Alberici, L., Corti, A., Gallo-Stampino, C., Traversari, C., and Doglioni, C.: Enhanced expression of CD13 in vessels of inflammatory and neoplastic tissues. J. Histochem. Cytochem. 59, 47 (2011).CrossRefGoogle ScholarPubMed
Saiki, I., Fujii, H., Yoneda, J., Abe, I.F., Nakajima, M., Tsuruo, T., and Azuma, I.: Role of aminopeptidase N (CD13) in tumor-cell invasion and extracellular matrix degradation. Int. J. Cancer Clin. Res. 54, 137 (2010).Google Scholar
Zhang, J., Xu, X., Shi, M., Chen, Y., Yu, D., Zhao, C., Gu, Y., Ynag, B., Guo, S., Ding, G., Jin, G., Wu, C-L., and Zhu, M.: CD13 Neutrophil-like myeloid-derived suppressor cells exert immune suppression through Arginase 1 expression in pancreatic ductal adenocarcinoma. Oncoimmunology 6, e1258504 (2017).CrossRefGoogle ScholarPubMed
Ikeda, N., Nakajima, Y., Tokuhara, T., Hattori, N., Sho, M., Kanehiro, H., and Miyake, M.: Clinical significance of aminopeptidase N/CD13 expression in human pancreatic carcinoma. Clin. Cancer Res. 9, 1503 (2003).Google ScholarPubMed
Zhang, Y., Zhang, H., Shi, W., and Wang, W.: Mief1 augments thyroid cell dysfunction and apoptosis through inhibiting AMPK-PTEN signaling pathway. J. Recept. Signal Transduct. Res. (2020). Available at: https://doi.org/10.1080/10799893.2020.1716799 (accessed December 23, 2019).CrossRefGoogle ScholarPubMed
Zakki, S.A., Muhammad, J.S., Li, J-L., Sun, L., Li, M-L., Feng, Q-W., Li, Y-L., Gui, Z-G., and Inadera, H.: Melatonin triggers the anticancer potential of phenylarsine oxide via induction of apoptosis through ROS generation and JNK activation. Metallomics (2020). Available at: https://doi.org/10.1039/C9MT00238C (accessed January 21, 2020).CrossRefGoogle ScholarPubMed
Wang, F., Wu, H., Fan, M., Yu, R., Zhang, Y., Liu, J., Zhou, X., Cai, Y., Huang, S., Hu, Z., and Jin, X.: Sodium butyrate inhibits migration and induces AMPK-mTOR pathway-dependent autophagy and ROS-mediated apoptosis via the miR-139-5p/Bmi-1 axis in human bladder cancer cells. FASEB J. (2020). Available at: https://doi.org/10.1096/fj.201902626R (accessed January 19, 2020).CrossRefGoogle ScholarPubMed
Li, P., Gao, L., Cui, T., Zhang, W., Zhao, Z., and Chen, L.: Cops5 safeguards genomic stability of embryonic stem cells through regulating cellular metabolism and DNA repair. Proc. Natl. Acad. Sci. U. S. A. (2020). Available at: https://doi.org/10.1073/pnas.1915079117 (accessed January 21, 2020).CrossRefGoogle ScholarPubMed
Medintz, I.L., Uyeda, H.T., Goldman, E.R., and Mattoussi, H.: Quantum dot bioconjugates for imaging, labelling and sensing. Nat. Mater. 4, 435 (2005).CrossRefGoogle Scholar
Wu, P. and Yan, X-P.: Doped quantum dots for chemo/biosensing and bioimaging. Chem. Soc. Rev. 42, 5489 (2013).CrossRefGoogle ScholarPubMed
Tian, B., Al-Jamal, W.T., Bossche, J.V.D., and Kostarelos, K.: Design and engineering of multifunctional quantum dot-based nanoparticles for simultaneous therapeutic-diagnostic applications. Nanostruct. Sci. Technol. (2012). Available at: https://doi.org/10.1007/978-1-4614-2305-8_16 (accessed February 1, 2012).CrossRefGoogle Scholar
Nurunnabi, M., Cho, K.J., Choi, J.S., Huh, K.M., and Lee, Y.K.: Targeted near-IR QDS-loaded micelles for cancer therapy and imaging. Biomaterials 31, 5436 (2010).CrossRefGoogle ScholarPubMed
Pan, J. and Feng, S.S.: Targeting and imaging cancer cells by folate-decorated, quantum dots (QDS)-loaded nanoparticles of biodegradable polymers. Biomaterials 30, 1176 (2009).CrossRefGoogle ScholarPubMed
Curnis, F., Arrigoni, G., Sacchi, A., Fischetti, L., and Corti, A.: Differential binding of drugs containing the ngr motif to CD13 isoforms in tumor vessels, epithelia, and myeloid cells. Cancer Res. 62, 867 (2002).Google ScholarPubMed
Bhagwat, S.V., Lahdenranta, J., Giordano, R.J., Arap, W., and Shapiro, L.H.: CD13/APN is activated by angiogenic signals and is essential for capillary tube formation. Blood 97, 652 (2001).CrossRefGoogle ScholarPubMed
Bhagwat, S.V., Petrovic, N., Okamoto, Y., and Shapiro, L.H.: The angiogenic regulator CD13/APN is a transcriptional target of RAS signaling pathways in endothelial morphogenesis. Blood 101, 1818 (2003).CrossRefGoogle ScholarPubMed
Kido, A., Krueger, S., Haeckel, C., and Roessner, A.: Inhibitory effect of antisense aminopeptidase N(APN/CDl3) cDNA transfection on the invasive potential of osteosarcoma cells. Clin. Exp. Metastasis 20, 585 (2003).CrossRefGoogle Scholar
Bauvois, B. and Dauzonne, D.: Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: Chemistry, biological evaluations, and therapeutic prospects. Med. Res. Rev. 26, 88 (2006).CrossRefGoogle ScholarPubMed
Dong, X., An, B., Salvucci Kierstead, L., Storkus, W.J., Amoscato, A.A., and Salter, R.D.: Modification of the amino terminus of a class II epitope confers resistance to degradation by CD13 on dendritic cells and enhances presentation to T cells. J. Immunol. 164, 129 (2000).CrossRefGoogle ScholarPubMed
Chen, Y., Wu, J-J., and Huang, L.: Nanoparticles targeted with NGR motif deliver c-myc siRNA and doxorubicin for anticancer therapy. Mol. Ther. 18, 828 (2010).CrossRefGoogle ScholarPubMed
Yokoyama, Y. and Ramakrishnan, S.: Addition of an aminopeptidase N-binding sequence to human endostatin improves inhibition of ovarian carcinoma growth. Cancer 104, 321 (2005).CrossRefGoogle ScholarPubMed
Svensen, N., Walton, J.G., and Bradley, M.: Peptides for cell-selective drug delivery. Trends Pharmacol. Sci. 33, 186 (2012).CrossRefGoogle ScholarPubMed
Corti, A., Curnis, F., Arap, W., and Pasqualini, R.: The neovasculature homing motif NGR: More than meets the eye. Blood 112, 2628 (2008).CrossRefGoogle ScholarPubMed
Curnis, F., Sacchi, A., Borgna, L., Magni, F., Gasparri, A., and Corti, A.: Enhancement of tumor necrosis factor alpha antitumor immunotherapeutic properties by targeted delivery to aminopeptidase N (CD13). Nat. Biotechnol. 18, 1185 (2000).CrossRefGoogle Scholar
Lees, E.E., Nguyen, T.L., Clayton, A.H., Muir, B.W., and Mulvaney, P.: The preparation of colloidally stable, water-soluble, biocompatible, semiconductor nanocrystals with a small hydrodynamic diameter. ACS Nano 3, 1121 (2009).CrossRefGoogle ScholarPubMed