Original Article

Targeted Gold Nanoparticles for Molecular CT Imaging of Breast Cancer: An In-Vitro Study

Abstract

Purpose: The incorporation of Nanoparticles (NPs) in Computed Tomography (CT) imaging significantly enhances the contrast, clarity, and sensitivity of CT scans, leading to a substantial improvement in the accuracy and reliability of diagnostic information obtained from the images. The objective of the current research was to investigate the application of gold (Au) NPs in enhancing the imaging capabilities of Breast Cancer (BC) cells.

Materials and Methods: Au NPs were synthesized by loading Trastuzumab (TZ) on PEGylated Au NPs. Firstly, Au NPs were produced and coated with PEG-SH to form PEG-Au NPs. Next, TZ was coupled with OPSS-PEG-SVA to enable its attachment to the PEG-Au NPs. The resulting NPs were characterized for their structure, size, and morphology using standard analytical techniques. To assess the potential of the developed NPs for CT scan imaging of BC cells, SKBr-3 cells were treated with Au NPs and TZ-PEG-Au NPs. Additionally, the cytotoxicity of the NPs was evaluated with the MTT technique.

Results: The SEM and TEM analyses revealed that the synthesized NPs exhibited a spherical shape and displayed a relatively uniform size distribution (approximately 45 nm). The results showed that the developed Au NPs have acceptable biocompatibility and superior X-ray attenuation properties compared to a commonly used contrast agent.

Conclusion: Based on our results, it can be concluded that the proposed TZ- Polyethylene Glycol-Au NPs are suitable for CT imaging of BC cells.

1- Ahmed M Afifi, Anas M Saad, Muneer J Al‐Husseini, Ahmed Osama Elmehrath, Donald W Northfelt, and Mohamad Bassam Sonbol, "Causes of death after breast cancer diagnosis: A US population‐based analysis." Cancer, Vol. 126 (No. 7), pp. 1559-67, (2020).
2- Zeinab Safarpour Lima, Mohammad Reza Ebadi, Ghazaleh Amjad, and Ladan Younesi, "Application of imaging technologies in breast cancer detection: a review article." Open Access Macedonian Journal of Medical Sciences, Vol. 7 (No. 5), p. 838, (2019).
3- Dolatkhah M Hashemzadeh N, Adibkia K, Aghanejad A, Barzegar-Jalali M, Omidi Y, Barar J, "Recent advances in breast cancer immunotherapy: The promising impact of nanomedicines." Life Sciences, Vol.;271:119110(2021 Apr 15).
4- Tarighatnia A Kadkhoda J, Tohidkia MR, Nader ND, Aghanejad A., "Photothermal therapy-mediated autophagy in breast cancer treatment: Progress and trends. Life sciences. 2022 Jun 1;298:120499.".
5- Luca Volterrani et al., "Dual-energy CT for locoregional staging of breast cancer: preliminary results." American Journal of Roentgenology, Vol. 214 (No. 3), pp. 707-14, (2020).
6- Ali Tarighatnia, Gurkaran Johal, Ayuob Aghanejad, Hossein Ghadiri, and Nader D Nader, "Tips and tricks in molecular imaging: a practical approach." Frontiers in Biomedical Technologies, Vol. 8 (No. 3), pp. 226-35, (2021).
7- Hedieh Mansouri et al., "A biocompatible theranostic nanoplatform based on magnetic gadolinium-chelated polycyclodextrin: in vitro and in vivo studies." Carbohydrate Polymers, Vol. 254p. 117262, (2021).
8- Ziyaee S, Malekzadeh R, Ghorbani M, Nasiri Motlagh B, Asghariazar V, and Mortezazadeh T, "Preparation of MnO2@ poly-(DMAEMA-co-IA)-conjugated methotrexate nano-complex for MRI and radiotherapy of breast cancer application." Magnetic Resonance Materials in Physics, Biology and Medicine, Vol. 36(5):779-95(2023).
9- Behnaz Babaye Abdollahi et al., "Main approaches to enhance radiosensitization in cancer cells by nanoparticles: A systematic review." Advanced Pharmaceutical Bulletin, Vol. 11 (No. 2), p. 212, (2021).
10- Tarighatnia A Jamshidi N, Ghaziyani MF, Sajadian F, Nader ND, " Folic acid-conjugated Fe-Au-based nanoparticles for dual detection of breast cancer cells by magnetic resonance imaging and computed tomography." Frontiers in Biomedical Technologies, Vol.;11(1):122-9(2024).
11- Reza Malekzadeh et al., "Nanoarchitecture-based photothermal ablation of cancer: a systematic review." Environmental Research, p. 116526, (2023).
12- Tarighatnia A Mohaghegh S, Omidi Y, Barar J, Aghanejad A, Adibkia K., "Multifunctional magnetic nanoparticles for MRI-guided co-delivery of erlotinib and L-asparaginase to ovarian cancer." Journal of Microencapsulation., (2022 May 19;39(4):394-408.).
13- Behnaz Babaye Abdollahi, Marjan Ghorbani, Hamed Hamishehkar, Reza Malekzadeh, and Alireza Farajollahi, "Synthesis and characterization of actively HER-2 Targeted Fe3O4@ Au nanoparticles for molecular radiosensitization of breast cancer." BioImpacts: BI, Vol. 13 (No. 1), p. 17, (2023).
14- Eun Hye Jeong, Giyoung Jung, Cheol Am Hong, and Hyukjin Lee, "Gold nanoparticle (AuNP)-based drug delivery and molecular imaging for biomedical applications." Archives of pharmacal research, Vol. 37pp. 53-59, (2014).
15- Wen S Li K, Larson AC, Shen M, Zhang Z, Chen Q, Shi X, Zhang G., "Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer." International journal of nanomedicine, Vol. 19:2589-600, (2013 Jul).
16- Petersen W Rayavarapu RG, Ungureanu C, Post JN, van Leeuwen T, Manohar S, "Synthesis and bioconjugation of gold nanoparticles as potential molecular probes for light-based imaging techniques." International Journal of biomedical imaging, Vol. 29817-1, (2007).
17- Hsu JC Bouché M, Dong YC, Kim J, Taing K, Cormode DP, "Recent advances in molecular imaging with gold nanoparticles." Bioconjugate chemistry., Vol. 4;31(2):303-14, (2019 Nov).
18- Iqbal N. Iqbal N, "Human epidermal growth factor receptor 2 (HER2) in cancers: overexpression and therapeutic implications." Molecular biology international., Vol. 2014.( 2014).
19- Shastry M Swain SM, Hamilton E, "Targeting HER2-positive breast cancer: advances and future directions." Nature reviews Drug discovery, Vol. 22(2):101-26. (2023 Feb).
20- Malekzadeh R, Babaye Abdollahi B, Ghorbani M, Pirayesh Islamian J, and Mortezazadeh T, "Trastuzumab conjugated PEG–Fe3O4@ Au nanoparticle as an MRI biocompatible nano-contrast agent." International Journal of Polymeric Materials and Polymeric Biomaterials, Vol. 3;72(10):759-70. (2023).
21- Motiei M Reuveni T, Romman Z, Popovtzer A, Popovtzer R., "Targeted gold nanoparticles enable molecular CT imaging of cancer: an in vivo study." International journal of nanomedicine., Vol. 11:2859-64. (2011 Nov ).
22- Lisha KP, Anshup, and Pradeep T, "Enhanced visual detection of pesticides using gold nanoparticles." Journal of Environmental Science and Health Part B, Vol. 16;44(7):697-705, (2009 Sep).
23- Mahmoudi G Tarighatnia A, Kiani M, Nader ND, "Current Challenges and New Opportunities of Hybrid Nanoparticles for Diagnosis and Treatment of Cancer." Frontiers in Biomedical Technologies, Vol. 1;11(1):1-5(2024 Jan).
24- Owoseni O Ejigah V, Bataille-Backer P, Ogundipe OD, Fisusi FA, Adesina SK, "Approaches to improve macromolecule and nanoparticle accumulation in the tumor microenvironment by the enhanced permeability and retention effect." Polymers, Vol. Jun 27;14(13):2601(2022).
25- Deb MK Khalkho BR, Kurrey R, Sahu B, Saha A, Patle TK, Chauhan R, Shrivas K., "Citrate functionalized gold nanoparticles assisted micro extraction of L-cysteine in milk and water samples using Fourier transform infrared spectroscopy " Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Vol. 15;267:120523.(2022 Feb ).
26- Suriyakala G Sathiyaraj S, Gandhi AD, Babujanarthanam R, Almaary KS, Chen TW, Kaviyarasu K., "Biosynthesis, characterization, and antibacterial activity of gold nanoparticles." Journal of Infection and Public Health, Vol. 1;14(12):1842-7(2021 Dec).
27- Merdan T Germershaus O, Bakowsky U, Behe M, Kissel T, "Trastuzumab− polyethylenimine− polyethylene glycol conjugates for targeting Her2-expressing tumors." Bioconjugate Chemistry, Vol. 20;17(5):1190-9(2006 Sep).
28- Tohidkia MR Siminzar P, Eppard E, Vahidfar N, Tarighatnia A, Aghanejad A., "Recent trends in diagnostic biomarkers of tumor microenvironment." Molecular Imaging and Biology, (2023 Jun;25(3):464-82.).
29- Chattopadhyay N Cai Z, Yang K, Kwon YL, Yook S, Pignol JP, Reilly RM., "111In-labeled trastuzumab-modified gold nanoparticles are cytotoxic in vitro to HER2-positive breast cancer cells and arrest tumor growth in vivo in athymic mice after intratumoral injection. Nuclear medicine and biology. 2016 Dec 1;43(12):818-26.".
30- Saung MT Galper MW, Fuster V, Roessl E, Thran A, Proksa R, Fayad ZA, Cormode DP., " Effect of computed tomography scanning parameters on gold nanoparticle and iodine contrast." Investigative radiology, Vol. 1;47(8):475-81(2012 Aug).
31- Kim EM Kim SH, Lee CM, Kim DW, Lim ST, Sohn MH, Jeong HJ, "Synthesis of PEG-iodine-capped gold nanoparticles and their contrast enhancement in in vitro and in vivo for X-ray/CT." Journal of Nanomaterials, Vol. 1;2012:46(2012 Jan).
32- Sarkar S Khademi S, Kharrazi S, Amini SM, Shakeri-Zadeh A, Ay MR, Ghadiri H., "Evaluation of size, morphology, concentration, and surface effect of gold nanoparticles on X-ray attenuation in computed tomography. Physica Medica. 2018 Jan 1;45:127-33.".
33- Abdkarimi MH Tarighatnia A, Nader ND, Mehdipour T, Fouladi MR, Aghanejad A, Ghadiri H., " Mucin-16 targeted mesoporous nano-system for evaluation of cervical cancer via dual-modal computed tomography and ultrasonography. New journal of chemistry." (2021;45(40):18871-80.).
34- Fouladi MR Tarighatnia A, Tohidkia MR, Johal G, Nader ND, Aghanejad A, Ghadiri H., "Engineering and quantification of bismuth nanoparticles as targeted contrast agent for computed tomography imaging in cellular and animal models." Journal of drug delivery science and technology, (2021 Dec 1;66:102895.).
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Keywords
Au Nanoparticles Polyethylene Glycol Molecular Imaging Computed Tomography Breast Cancer Cells

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1.
Kheradmand N, Talaee O, Tabatabaee F, Alvandi V, Khoshdel E, Ghadimi P, ÇAĞLAR M. Targeted Gold Nanoparticles for Molecular CT Imaging of Breast Cancer: An In-Vitro Study. Frontiers Biomed Technol. 2024;.