Biodegradable Radiofrequency Responsive Nanoparticles for Augmented Thermal Ablation Combined with Triggered Drug Release in Liver Tumors

Abstract

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.

Effective Cancer Theranostics with Polymer Encapsulated Superparamagnetic Nanoparticles: Combined Effects of Magnetic Hyperthermia and Controlled Drug Release

“…Our previous works on LSMO demonstrated that surface-grafted (colloidally stable) particles are capable of generating efficient thermal dose within a precisely controlled time duration. , This strategy was further exploited to develop stable, dispersible, cyto-hemocompatible PM@SPMNPs (i.e., PEG capped La 0.7 Sr 0.3 MnO 3 MNPs) with 6-fold improved SAR compared to their pristine counterpart. The enhancement of SAR and stimulated drug delivery resulted in an efficient internalization of drug by efficient thermal dose and the consequent increased cancer cell deaths. , Nevertheless, the results presented herein show that multimodality, i.e., DOX delivery (chemotherapy) with MFH (magneto-thermotherapy) using PM@SPMNPs is more effective than using single modality …”

“…The enhancement of SAR and stimulated drug delivery resulted in an efficient internalization of drug by efficient thermal dose and the consequent increased cancer cell deaths. 37,38 Nevertheless, the results presented herein show that multimodality, i.e., DOX delivery (chemotherapy) with MFH (magneto-thermotherapy) using PM@SPMNPs is more effective than using single modality. 26 As it is known that certain NPs are highly effective but also toxic to patients, we performed a preliminary histopathological examination of exposed mice organs focusing on tissue damage, inflammation or lesions (Figure 6).…”

Remotely Triggered Nano-Theranostics For Cancer Applications

“…An additional study showed that biodegradable alginate nanoparticles combining radiofrequency triggered hyperthermia and triggered doxorubicin release could be used as an effective combination treatment method. In orthotopic rat liver tumor models, there was enhanced thermal ablation, controlled doxorubicin release, and imaging potential using MRI 150 . X-ray induced ionizing radiation and radiofrequency triggered hyperthermia are only a couple examples of some additional remotely triggered treatments that could be used in theranostic platforms.…”

Magnetic drug delivery systems

“…In recent years, integrated medical material for both diagnosis and simultaneous treatment has also become very attractive for doctors and patients because it can save a great deal of time and money. Based on this requirement, MNPs, previously used as a powerful diagnostic tool, are being considered as theranostic delivery systems combining imaging agents and effective therapeutic drugs [5][6][7][8][9].…”