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.
Radiofrequency
ablation (RFA) and doxorubicin (Dox) chemotherapy
are separately approved for liver cancer therapy; however, both have
limited success in the clinic due to suboptimal/nonuniform heating
and systemic side effects, respectively. Here, we report a biodegradable
nanoparticle (NP) system showing excellent RF hyperthermic response
together with the ability to locally deliver Dox in the liver under
RF trigger and control. The nanosystem was prepared by doping a clinically
permissible dose (∼4.3 wt %, 0.03 ppm) of stannous ions in
alginate nanoparticles (∼100 nm) coloaded with Dox at ∼13.4
wt % concentration and surface conjugated with galactose for targeting
asialo-glycoprotein receptors in liver tumors. Targeted NP-uptake
and increased cytotoxicity when combined with RF exposure was demonstrated
in HEPG2 liver cancer cells. Following in vitro (chicken liver phantom)
demonstration of locally augmented RF thermal response, in vivo scintigraphic
imaging of 99Tc-labeled NPs was performed to optimize liver
localization in Sprague–Dawley (SD) rats. RF ablation was performed
in vivo using a cooled-tip probe, and uniformly enhanced (∼44%)
thermal ablation was demonstrated with magnetic resonance imaging
along with RF-controlled Dox release. In orthotopic rat liver tumor
models, real-time infrared imaging revealed significantly higher (∼20
°C) RF thermal response at the tumor site, resulting in uniform
augmented ablation (∼80%) even at a low RF power exposure of
15 W for just 1 min duration. Being a clinically acceptable, biodegradable
material, alginate nanoparticles hold strong translational potential
for augmented RF hyperthermia combined with triggered drug release.
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