Perovskite nanoparticles as contrast agents for molecular imaging and anti-cancer theranostics

AL Habsi, Salim Khalfan Suroor

Abstract

Nanoparticles (NPs) offer diagnostic and therapeutic capabilities not accessible with microscale particles. As the field of molecular imaging has risen up out of the mixing of molecular biology with medicinal imaging, the use of NPs as imaging contrast agents is progressively increasing. Super paramagnetic iron oxide (SPIONs) are investigated and used as T2 contrasting agents for MRI respectively, due to their paramagnetic properties. Contrast agents are used to highlight the targeted tumour regions in the molecular tissues in order to offer a great visibility, either lighter or darker during MRI diagnosis. Typically, SPION influence T2 relaxation time of the water molecules protons, whereas Gd-based complexes are the main contrast agents influencing T1 relaxation type. However, SPIONs present some drawbacks such as difficulties in distinguishing molecular regions with weak signals based on a bright contrast. Several efforts are being devoted towards construct T1 and T2 dual-modes contrast agents to overcome the disadvantages of the single contrast agents modalities. Hence, a synergetic combination of T1 and T2 contrast enhanced imaging can potentially offer more detailed and comprehensive imaging information which provide higher diagnostic accuracy.
The aim of the present study is to prepare perovskite mixed metal compounds with general formula KMF3 (M = Mn, Fe, Co) and test their applicability as contrast agents. The advantage of using perovskite mixed metal compounds is that their crystal structure and formulas offer flexibility for chemical modification, thus tuning of magnetic properties and, therefore, improved contrast agents. Furthermore, KMnF3 has been reported as a biocompatible, promising T1 contrast agent.
NPs of KMF3 (M =Mn, Fe, Co) were prepared via co-precipitation (bare NPs) and solvothermal methods (oleate-capped NPs). Powder x-ray diffraction (PXRD), and TEM analysis were undertaken to determine the crystal structure and the particle size. To allow for compatibility in aqueous medium, the NPs were functionalised with a variety of ligands such as 11-aminoundecanoic acid, alendronic acid, polyethylene glycol (PEG) and oleylamine. IR spectroscopy was utilised to ascertain the occurrence of functionalisation.
Both methods were effective in synthesising KMF3 (M=Mn, Fe, Co) NPs with cubic unit cell, although some impurities are present when oleate-capped NPs are prepared via solvothermal method.
NPs obtained via co-precipitation underwent decomposition during the functionalisation process with 11-aminoundecanoic acid, alendronic acid and PEG ligands. NPs obtained via solvothermal methods showed improved stability under the ligand exchange process with oleylamine ligand, leading to functionalisation with alendronic acid.
Ultra-small nanoparticles (USNPs) with an average hydrodynamic diameter of 2 nm were obtained thanks to the tuning of the synthetic method. In-vitro MRI test showed a unique dual mode weighted T1 and T2 MR imaging effect for KMnF3 with relatively high relaxivity (r1) and moderately high (r2) of 6 and 51 mM-1s-1 respectively. These values are comparable to that of the Gd-based complexes and SPIONs. Functionalised KFeF3 NPs were unstable and, at some stage during the characterisation, decomposed partially to Fe3O4 in air, while KCoF3 showed a negative MRI effect.
Using the developed T1/T2 dual-mode coated alendronate KMnF3 a theranostic system was developed via a successful conjugation process to DOX, a drug used in chemotherapy to treat various types of cancers. Furthermore, conjugation to the over expressed VEGFR anti-body to specifically target VEGFR, the over expressed protein in cervical and colorectal cancer cell lines was successfully achieved.
After a successful detection of VEGFR and EGFER in cervical (HeLa) and colorectal (HT-29 and HCT-116) cancer cell lines, the toxicity of the new theranostic system was tested against these cell lines using MTS colorimetric test. The cells uptake and localisation of the NPs were evaluated by fluorescence using flow cytometry and confocal microscopy.

Citation

AL Habsi, S. K. S. (2019). Perovskite nanoparticles as contrast agents for molecular imaging and anti-cancer theranostics. (Thesis). University of Hull. Retrieved from https://hull-repository.worktribe.com/output/4223738

• Thesis Type: Thesis
• Deposit Date: Dec 9, 2021
• Publicly Available Date: Feb 24, 2023
• Keywords: Chemistry
• Public URL: https://hull-repository.worktribe.com/output/4223738
• Additional Information: Department of Chemistry, The University of Hull
• Award Date: Sep 1, 2019