Biomineral Nano-Theranostic agent for Magnetic Resonance Image Guided, Augmented Radiofrequency Ablation of Liver Tumor

Abstract

Theranostic nanoparticles based on biocompatible mineral compositions can significantly improve the translational potential of image guided cancer nano-therapy. Here, we report development of a single-phase calcium phosphate biomineral nanoparticle (nCP) with dual-mode magnetic resonance contrast (T1-T2) together with radiofrequency (RF) mediated thermal response suitable for image-guided RF ablation of cancer. The nanoparticles (NP) are engineered to provide dual MR contrast by an optimized doping concentration (4.1 at%) of paramagnetic ion, Fe3+, which also renders lossy dielectric character for nCP leading to thermal response under RF exposure. In vivo compatibility and dual-mode MR contrast are demonstrated in healthy rat models. MRI and T2 mapping suggest hepatobiliary clearance by ~96 hours. MRI guided intratumoral injection in subcutaneous rat glioma and orthotopic liver tumor models provide clear visualization of NP in MRI which also helps in quantifying NP distribution within tumor. Furthermore, by utilising RF mediated thermal response, NP treated tumor could be ablated using clinically approved RF ablation system (10 W,13.3 GHz). Real-time in vivo thermal imaging exhibits 119 ± 10% increase in temperature change (ΔT) for NP treated orthotopic liver tumor (ΔT = 51.5 ± 2 °C), compared to untreated healthy liver control (ΔT = 21.5 ± 2 °C). In effect, we demonstrate a promising nano-biomineral theranostic agent for dual-mode MRI combined with radiofrequency ablation of solid tumors.

Remotely Activated Nanoparticles for Anticancer Therapy

“…The iron doping causes a characteristic augmented ionic conductance which increases the dielectric loss of the NPs under the RF stimulation. This effect provokes a temperature rise responsible of the observed necrosis [86].…”

Adipose derived mesenchymal stem cell secretome formulation as a biotherapeutic to inhibit growth of drug resistant triple negative breast cancer

“…While our previous work has focused on targeted therapy 1 and drug delivery systems 2 to find new solutions for cancer therapy, in this work we consider the use of an innovative biotherapeutic approach using the therapeutic potential of stem cell secretions and creating a new formulation with translational potential. In this study, we use in vitro and in vivo models of triple negative breast cancer 3 (TNBC) lacking estrogen, progesterone and human epidermal growth factor 2 (HER2) receptors which is an aggressive form of breast cancer showing chemo 4 , 5 and immune resistant phenotype with poor response to targeted therapies 6 , 7 to evaluate the anti-cancer potential.…”

Iron (III)-Quercetin Complex: Synthesis, Physicochemical Characterization, and MRI Cell Tracking toward Potential Applications in Regenerative Medicine

“…The lower-level values of the saturation magnetization of IronQ were responsible as a T1-positive contrast (bright image) agent for magnetic resonance imaging (MRI). T1-positive contrast agents, such as gadopentetate dimeglumine (Magnevist®), revealed Ms values equal to 0.397 emu/g at 1.2 T (12 kOe), while the Gd (III)-quercetin complex revealed Ms values equal to 0.405 emu/g at 1.5 T, and the iron (III)-doped calcium phosphate nanoparticles revealed Ms values that were lower than 0.15 emu/g at 1.5 T [ 71 – 73 ]. Notably, the higher levels (>20 emu/g) of the contrast agents, particularly superparamagnetic iron oxide nanoparticles (SPIONs), were observed as a superparamagnetic property and exhibited T2 negative (contrast dark image) in MR imaging [ 71 , 74 ].…”

“…The paramagnetic properties of IronQ in the case study may be related to the five unpaired electrons found in the 3d orbit of iron (III) (high spin, S = 5/2), leading to an apparent effect identified as spin-lattice interactions under longitudinal relaxation at the applied magnetic field [ 73 ]. However, the oxidative state of iron (II) without the magnetic property did not affect T1 relaxation.…”