Tohid Mortezazadeh1, Elham Gholibegloo2, Nader Riyahi Alam3,4, Sadegh Dehghani5, Soheila Haghgoo6, Hossein Ghanaati6,7, Mehdi Khoobi8,9. 1. Department of Medical Physic, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Biomaterials Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, 1417614411, Tehran, Iran. 3. Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran. mehdi.khoobi@gmail.com. 4. Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. mehdi.khoobi@gmail.com. 5. Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran. 6. Pharmaceutical Department, Food and Drug Laboratory Research Center, Food and Drug Organization (FDO), Ministry of Health, Imam St., Valiasr Cross, Tehran, 1113615911, Iran. 7. Medical Imaging Center, Imam Hospital Complex, School of Medicine, Tehran University of Medical Sciences (TUMS), Keshavarz Blvd, Tehran, 1419733141, Iran. 8. Biomaterials Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, 1417614411, Tehran, Iran. riahialam@gmail.com. 9. Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. riahialam@gmail.com.
Abstract
OBJECTIVES: In this study, a novel targeted MRI contrast agent was developed by coating gadolinium oxide nanoparticles (Gd2O3 NPs) with β-cyclodextrin (CD)-based polyester and targeted by folic acid (FA). MATERIALS AND METHODS: The developed Gd2O3@PCD-FA MRI contrast agent was characterized and evaluated in relaxivity, in vitro cell targeting, cell toxicity, blood compatibility and in vivo tumor MR contrast enhancement. RESULTS: In vitro cytotoxicity and hemolysis assays revealed that Gd2O3@PCD-FA NPs have no significant cytotoxicity after 24 and 48 h against normal human breast cell line (MCF-10A) at concentration of up to 50 µg Gd+3/mL and have high blood compatibility at concentration of up to 500 µg Gd+3/mL. In vitro MR imaging experiments showed that Gd2O3@PCD-FA NPs enable targeted contrast T1- and T2-weighted MR imaging of M109 as overexpressing folate receptor cells. Besides, the in vivo analysis indicated that the maximum contrast-to-noise ratio (CNR) of tumor in mice increased after injection of Gd2O3@PCD-FA up to 5.89 ± 1.3 within 1 h under T1-weighted imaging mode and reduced to 1.45 ± 0.44 after 12 h. While CNR increased up to maximum value of 1.98 ± 0.28 after injection of Gd2O3@PCD within 6 h and reduced to 1.12 ± 0.13 within 12 h. CONCLUSION: The results indicate the potential of Gd2O3@PCD-FA to serve as a novel targeted nano-contrast agent in MRI.
OBJECTIVES: In this study, a novel targeted MRI contrast agent was developed by coating gadolinium oxide nanoparticles (Gd2O3 NPs) with β-cyclodextrin (CD)-based polyester and targeted by folic acid (FA). MATERIALS AND METHODS: The developed Gd2O3@PCD-FA MRI contrast agent was characterized and evaluated in relaxivity, in vitro cell targeting, cell toxicity, blood compatibility and in vivo tumor MR contrast enhancement. RESULTS: In vitro cytotoxicity and hemolysis assays revealed that Gd2O3@PCD-FA NPs have no significant cytotoxicity after 24 and 48 h against normal human breast cell line (MCF-10A) at concentration of up to 50 µg Gd+3/mL and have high blood compatibility at concentration of up to 500 µg Gd+3/mL. In vitro MR imaging experiments showed that Gd2O3@PCD-FA NPs enable targeted contrast T1- and T2-weighted MR imaging of M109 as overexpressing folate receptor cells. Besides, the in vivo analysis indicated that the maximum contrast-to-noise ratio (CNR) of tumor in mice increased after injection of Gd2O3@PCD-FA up to 5.89 ± 1.3 within 1 h under T1-weighted imaging mode and reduced to 1.45 ± 0.44 after 12 h. While CNR increased up to maximum value of 1.98 ± 0.28 after injection of Gd2O3@PCD within 6 h and reduced to 1.12 ± 0.13 within 12 h. CONCLUSION: The results indicate the potential of Gd2O3@PCD-FA to serve as a novel targeted nano-contrast agent in MRI.
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