Arg-Gly-Asp-D-Phe-Lys Peptide-modified PEGylated Dendrimer-entrapped Gold Nanoparticles for Targeted Computed Tomography Imaging of Breast Carcinoma

Overview

Journal Nanomedicine (Lond)

Specialty Biotechnology

Date 2015 Jul 28

PMID 26214356

Citations 4

Authors

Kangan Li

Zhuoli Zhang

Linfeng Zheng

Hong Liu

Wei Wei

Zhiyu Li

Zhiyan He

Andrew C Larson

Guixiang Zhang

Affiliations

Soon will be listed here.

Abstract

Aim: To investigate cyclo (Arg-Gly-Asp-D-Phe-Lys) peptide (RGD)-modified PEGylated dendrimer-entrapped gold nanoparticles (PEGylated Au DENPs-RGD) for targeted computed tomography (CT) imaging of breast carcinomas.

Materials & Methods: PEGylated Au DENPs-RGD were synthesized and characterized. Then, the PEGylated Au DENPs-RGD for targeted CT imaging were investigated using the MDA-MB-435 cell line, an integrin-rich breast carcinoma cells, and mice with MDA-MB-435 xenograft tumors. Finally, silver enhancement staining and integrin αvβ3 immunohistochemistry of the tumors were performed.

Results: The synthesized PEGylated Au DENPs-RGD were spherical, water dispersible and biocompatible nanoprobes with a gold nanoparticle core size of 2.8 nm. Due to the presence of the Au nanoparticles, the PEGylated Au DENPs-RGD displayed a higher x-ray attenuation intensity than Omnipaque at the same Au or I concentrations. The conjugated RGD ligand can specifically identify and target overexpressed integrin receptors on MDA-MB-435 cells. After intravenous injection, these nanoprobes accumulated in the targeted area of mice with MDA-MB-435 xenograft tumors, which enabled the tumor to be detected by CT imaging. The histological results confirmed the imaging results.

Conclusion: The PEGylated Au DENPs-RGD can be used as targeted nanoprobes with good biocompatibility for targeted CT imaging and diagnosis of integrin-positive tumors.

Citing Articles

Targeting Ultrasmall Gold Nanoparticles with cRGD Peptide Increases the Uptake and Efficacy of Cytotoxic Payload.

Perrins R, McCarthy L, Robinson A, Spry K, Cognet V, Ferreira A Nanomaterials (Basel). 2022; 12(22).

PMID: 36432299 PMC: 9696180. DOI: 10.3390/nano12224013.

Integrin-Targeting Peptides for the Design of Functional Cell-Responsive Biomaterials.

Zhao J, Santino F, Giacomini D, Gentilucci L Biomedicines. 2020; 8(9).

PMID: 32854363 PMC: 7555639. DOI: 10.3390/biomedicines8090307.

A review of molecular imaging of atherosclerosis and the potential application of dendrimer in imaging of plaque.

Anwaier G, Chen C, Cao Y, Qi R Int J Nanomedicine. 2017; 12:7681-7693.

PMID: 29089763 PMC: 5656339. DOI: 10.2147/IJN.S142385.

Development of nanoparticle-based optical sensors for pathogenic bacterial detection.

Mocan T, Matea C, Pop T, Mosteanu O, Buzoianu A, Puia C J Nanobiotechnology. 2017; 15(1):25.

PMID: 28359284 PMC: 5374694. DOI: 10.1186/s12951-017-0260-y.

References

Jiang X, Sha X, Xin H, Chen L, Gao X, Wang X . Self-aggregated pegylated poly (trimethylene carbonate) nanoparticles decorated with c(RGDyK) peptide for targeted paclitaxel delivery to integrin-rich tumors. Biomaterials. 2011; 32(35):9457-69. DOI: 10.1016/j.biomaterials.2011.08.055. View

Dixit S, Novak T, Miller K, Zhu Y, Kenney M, Broome A . Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors. Nanoscale. 2014; 7(5):1782-90. PMC: 4437576. DOI: 10.1039/c4nr04853a. View

Danhier F, Le Breton A, Preat V . RGD-based strategies to target alpha(v) beta(3) integrin in cancer therapy and diagnosis. Mol Pharm. 2012; 9(11):2961-73. DOI: 10.1021/mp3002733. View

Liu H, Shen M, Zhao J, Guo R, Cao X, Zhang G . Tunable synthesis and acetylation of dendrimer-entrapped or dendrimer-stabilized gold-silver alloy nanoparticles. Colloids Surf B Biointerfaces. 2012; 94:58-67. DOI: 10.1016/j.colsurfb.2012.01.019. View

Liu Z, Cai W, He L, Nakayama N, Chen K, Sun X . In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. Nat Nanotechnol. 2008; 2(1):47-52. DOI: 10.1038/nnano.2006.170. View

Shen M, Shi X . Dendrimer-based organic/inorganic hybrid nanoparticles in biomedical applications. Nanoscale. 2010; 2(9):1596-610. DOI: 10.1039/c0nr00072h. View

Kukowska-Latallo J, Candido K, Cao Z, Nigavekar S, Majoros I, Thomas T . Nanoparticle targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer. Cancer Res. 2005; 65(12):5317-24. DOI: 10.1158/0008-5472.CAN-04-3921. View

Kobayashi H, Longmire M, Ogawa M, Choyke P, Kawamoto S . Multiplexed imaging in cancer diagnosis: applications and future advances. Lancet Oncol. 2010; 11(6):589-95. PMC: 3412687. DOI: 10.1016/S1470-2045(10)70009-7. View

Peng C, Li K, Cao X, Xiao T, Hou W, Zheng L . Facile formation of dendrimer-stabilized gold nanoparticles modified with diatrizoic acid for enhanced computed tomography imaging applications. Nanoscale. 2012; 4(21):6768-78. DOI: 10.1039/c2nr31687k. View

10.

Dreaden E, Austin L, Mackey M, El-Sayed M . Size matters: gold nanoparticles in targeted cancer drug delivery. Ther Deliv. 2012; 3(4):457-78. PMC: 3596176. DOI: 10.4155/tde.12.21. View

11.

Yu M, Park J, Jon S . Targeting strategies for multifunctional nanoparticles in cancer imaging and therapy. Theranostics. 2012; 2(1):3-44. PMC: 3263514. DOI: 10.7150/thno.3463. View

12.

Reuveni T, Motiei M, Romman Z, Popovtzer A, Popovtzer R . Targeted gold nanoparticles enable molecular CT imaging of cancer: an in vivo study. Int J Nanomedicine. 2011; 6:2859-64. PMC: 3224712. DOI: 10.2147/IJN.S25446. View

13.

Taherian A, Li X, Liu Y, Haas T . Differences in integrin expression and signaling within human breast cancer cells. BMC Cancer. 2011; 11:293. PMC: 3146943. DOI: 10.1186/1471-2407-11-293. View

14.

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

15.

Kim D, Park S, Lee J, Jeong Y, Jon S . Antibiofouling polymer-coated gold nanoparticles as a contrast agent for in vivo X-ray computed tomography imaging. J Am Chem Soc. 2007; 129(24):7661-5. DOI: 10.1021/ja071471p. View

16.

Rabin O, Perez J, Grimm J, Wojtkiewicz G, Weissleder R . An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles. Nat Mater. 2006; 5(2):118-22. DOI: 10.1038/nmat1571. View

17.

Shi X, Thomas T, Myc L, Kotlyar A, Baker Jr J . Synthesis, characterization, and intracellular uptake of carboxyl-terminated poly(amidoamine) dendrimer-stabilized iron oxide nanoparticles. Phys Chem Chem Phys. 2007; 9(42):5712-20. DOI: 10.1039/b709147h. View

18.

Liu H, Xu Y, Wen S, Chen Q, Zheng L, Shen M . Targeted tumor computed tomography imaging using low-generation dendrimer-stabilized gold nanoparticles. Chemistry. 2013; 19(20):6409-16. DOI: 10.1002/chem.201204612. View

19.

Zitzmann S, Ehemann V, Schwab M . Arginine-glycine-aspartic acid (RGD)-peptide binds to both tumor and tumor-endothelial cells in vivo. Cancer Res. 2002; 62(18):5139-43. View

20.

Li K, Wen S, Larson A, Shen M, Zhang Z, Chen Q . Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer. Int J Nanomedicine. 2013; 8:2589-600. PMC: 3722039. DOI: 10.2147/IJN.S46177. View